WO2025111235A1

WO2025111235A1 - Phosphor compositions with improved radioimaging characteristics and methods for preparing the same

Info

Publication number: WO2025111235A1
Application number: PCT/US2024/056460
Authority: WO
Inventors: Zakaryae Fathi; JR Wayne BEYER; Harold Walder
Original assignee: Immunolight LLC
Current assignee: Immunolight LLC
Priority date: 2023-11-21
Filing date: 2024-11-19
Publication date: 2025-05-30
Anticipated expiration: 2026-05-21

Abstract

Methods for enhancing the radioimaging of energy modulation agents, to better enable their detection within the body once administered are provided, involving the use of dopants in coatings or in the energy modulation agents themselves, the preparation of mixtures or composite particles of the energy modulation agents with high atomic mass materials, or the use of contrast agents as coatings on the energy modulation agents, and the products produced by the methods.

Description

ATTORNEY DOCKET: 018607-161990 TITLE OF THE INVENTION PHOSPHOR COMPOSITIONS WITH IMPROVED RADIOIMAGING CHARACTERISTICS AND METHODS FOR PREPARING THE SAME CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present application is related to, and claims priority to, U.S. Provisional Application Serial No.63/601,487, filed November 21, 2023, the contents of which are hereby incorporated by reference in their entirety. BACKGROUND OF THE INVENTION FIELD OF THE INVENTION [0002] The present invention relates to methods for enhancing the radioimaging of a coated energy modulation agent, and the compositions produced by the method. DESCRIPTION OF THE RELATED ART [0003] Light modulation from a deeply penetrating radiation like X-ray opens the possibility for activating bio-therapeutic agents of various kinds within mammalian bodies. Other possibilities include the activation of photo-catalysts in mediums for cross-linking reactions in polymeric chains and polymer based adhesives. These examples are but two examples of a number of possibilities that can be more generally described as the use of a conversion material to convert an initiating radiation that is deeply penetrating to another useful radiation possessing the capability of promoting photo-based chemical reactions. The photo-chemistry is driven inside mediums of far ranging kinds including organic, inorganic or composited from organic and inorganic materials. [0004] The photo-activation with no line of site required can be done in-vivo and ex-vivo such as those carried out in cell cultures. In turn, the photo activation of select bio- therapeutic agent, and conceivably more than one agent at a time, can lead to the onset of a desirable chemical reaction, or a cascade of reactions, that in turn lead to a beneficial therapeutic outcome. As an example, the binding of psoralen to DNA through the formation of monoadducts is well known to engender an immune response if done properly. An in- depth treatise of the subject is available in the open literature. Psoralen under the correct 6240479.1 photo-catalytic light gains the aptitude to bind to DNA. Psoralen has been reported to react to other sites that have a suitable reactivity including and not limited to cell walls. If this reaction is of the correct kind, as is the case for psoralen-DNA monoadducts formation, the binding leads to a programmable cell death referred to as Apoptosis. Such programmable cell death, if accomplished over a sufficiently large cell population, can signal the body to mount an immune response enabling target specific cell kill throughout the body. Such immune response is of the upmost importance for various medical treatments including cancer cure. [0005] The cascade of events described above has at its source the modulation of electromagnetic energy from the X-ray to the UV energy using phosphors in the presence of bio-therapeutic agents; these methods and the like, have been thoroughly described in various patents and patent applications such as those listed in the cross-reference section above. [0006] In particular, in U.S. Serial No.11/935,655, entitled “METHODS AND SYSTEMS FOR TREATING CELL PROLIFERATION DISORDERS,” the use of a phosphorescent emitting source was described with the advantage of phosphorescent emitting molecules or other source may be electroactivated or photoactivated prior to insertion into the tumor either by systemic administration or direct insertion into the region of the tumor. Phosphorescent materials have longer relaxation times than fluorescent materials. Energy emission is delayed or prolonged from a fraction of a second to several hours. Otherwise, the energy emitted during phosphorescent relaxation is not otherwise different than fluorescence, and the range of wavelengths may be selected by choosing a particular phosphor. [0007] In particular, in U.S. Serial No.12/401,478, entitled “PLASMONIC ASSISTED SYSTEMS AND METHODS FOR INTERIOR ENERGY-ACTIVATION FROM AN EXTERIOR SOURCE,” the use of phosphorescent materials as energy modulation agents was described. The ‘478 application details a number of modulation agents some having a very short energy retention time (on the order of fs-ns, e.g. fluorescent molecules) whereas others having a very long half-life (on the order of seconds to hours, e.g. luminescent inorganic molecules or phosphorescent molecules). Specific types of energy modulation agents described in the ‘478 application included Y2O3; ZnS; ZnSe; MgS; CaS; Mn, Er ZnSe; Mn, Er MgS; Mn, Er CaS; Mn, Er ZnS; Mn,Yb ZnSe; Mn,Yb MgS; Mn, Yb CaS; Mn,Yb ZnS:Tb³⁺, Er³⁺; ZnS:Tb³⁺; Y2O3:Tb³⁺; Y2O3:Tb³⁺, Er3⁺; ZnS:Mn²⁺; ZnS:Mn,Er³⁺. [0008] Presently, light (i.e., electromagnetic radiation from the radio frequency through the visible to the x-ray and gamma ray wavelength range) activated processing is also used in a number of industrial processes ranging from photoresist curing, to on-demand ozone production, to sterilization, to the promotion of polymer cross-linking activation (e.g. in 2 6240479.1 adhesive and surface coatings) and others. Today, light activated processing is seen in these areas to have distinct advantages over more conventional approaches. For example, conventional sterilization by steam autoclaving or in food processing by pasteurization may unsuitably overheat the medium to be sterilized. As such, light activated curable coatings are one of the fastest growing sectors in the coatings industry. In recent years, this technology has made inroads into a number of market segments like fiber optics, optical and pressure- sensitive adhesives, and automotive applications like cured topcoats, and curable powder coatings. The driving force of this development is mostly the quest for an increase in productivity of the coating and curing process, as conventional non light activated adhesive and surface coatings typically require 1) the elimination of solvents from the adhesive and surface coatings to produce a cure and 2) a time/temperature cure which adds delay and costs to the manufacturing process. [0009] Moreover, the use of solvent based products in adhesive and surface coatings applications is becoming increasingly unattractive because of rising energy costs and stringent regulation of solvent emissions into the atmosphere. Optimum energy savings as well as beneficial ecological considerations are both served by radiation curable adhesive and surface coating compositions. Radiation curable polymer cross-linking systems have been developed to eliminate the need for high oven temperatures and to eliminate the need for expensive solvent recovery systems. In those systems, light irradiation initiates free-radical cross-linking in the presence of common photosensitizers. [0010] However, in the adhesive and surface coating applications and in many of the other applications listed above, the light-activated processing is limited due to the penetration depth of light into the processed medium. For example, in water sterilization, ultraviolet light sources are coupled with agitation and stirring mechanisms in order to ensure that any bacteria in the water medium will be exposed to the UV light. In light-activated adhesive and surface coating processing, the primary limitation is that the material to be cured must be directly exposed to the light, both in type (wavelength or spectral distribution) and intensity. In adhesive and surface coating applications, any “shaded” area will require a secondary cure mechanism, increasing cure time over the non-shaded areas and further delaying cure time due to the existent of a sealed skin through which subsequent curing must proceed (i.e., referred to as a cocoon effect). [0011] In each of the above noted industries and treatments, one issue that arises is the distribution of the light emitters within a medium (whether in living tissue such as a tumor or in a commercial setting such as in an adhesive or resin), and how to better ensure that the 3 6240479.1 light emitters are well distributed. When such the light emitters used are an energy modulation agent (in vivo in a patient or without line of sight in an industrial activation) which converts applied energy into an emitted energy of the desired wavelength, the amount of emission output from the energy modulation agent becomes one factor to success, while the ability to radioimage that energy modulation agent and detect its distribution within the medium is a further factor for success. In certain instances, the energy modulation agent must be coated with a biocompatible coating to ensure biocompatibility with the medium (typically a living subject or patient). SUMMARY OF THE INVENTION [0012] Accordingly, one object of the present invention is to provide methods to enhance the radioimaging of an energy modulation agent, which may or may not have a coating with high transmissibility at the emission wavelength. [0013] A further object of the present invention is to provide such methods for an energy modulation agent having a diamond or diamond-like carbon coating. [0014] A further object of the present invention is to provide energy modulation agents prepared by the method of the invention which have significantly enhanced radioimaging capability. These and other objects of the invention, alone or in combinations, have been satisfied by the discovery of methods for enhancing radioimaging of an energy modulation agent, comprising: (i) coating a dried energy modulation agent with a coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, wherein the coating comprises one or more contrast agents in an amount sufficient to enhance radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent, and the coated energy modulation agents produced thereby; or (ii) coating a dried energy modulation agent with a first coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, and applying a second coating on the first coating, wherein the second coating comprises one or more contrast agents, wherein the second coating enhances radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent; or (iii) forming a coating on a surface of particles of the energy modulation agent, wherein the coating comprises one or more contrast agents; or (iv) forming a crystalline energy modulation agent having incorporated therein an imageable 4 6240479.1 amount of one or more high atomic mass dopants in a crystalline lattice of the crystalline energy modulation agent; or (v) mixing a first plurality of particles comprising one or more energy modulation agents with a second plurality of particles comprising one or more high atomic mass materials to provide the energy modulation agent particle mixture having enhanced radioimageability; or (vi) providing a dispersed particle mixture comprising a first plurality of particles of one or more energy modulation agents and a second plurality of particles of one or more high atomic mass materials; and mixing the dispersed particle mixture with a polymer binder to encapsulate one or more of the first plurality of particles and one or more of the second plurality of particles within the polymer binder, thus providing a plurality of energy converting composite particles each containing one or more energy modulation agents and one or more high atomic mass materials; and products produced thereby. BRIEF DESCRIPTION OF THE DRAWINGS [0015] A more complete appreciation of the invention and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein: [0016] Figs.1A and 1B provide graphical representations of a crystalline material along a crystalline plane, with each dot representing one atom in the crystalline matrix (Fig.1A), and the same crystalline material, but containing dopant elements having a high atomic mass (represented by the dots having an “X” through them) which are doped by substitution in the crystalline lattice (Fig.1B). [0017] Figs.2A and 2B provide graphical representations of a low atomic mass energy converting particle (20) with a surface coating (22), such as a DLC coating, for example, without the dopant (22a) (Figure 2A) and with the dopant (22b) (Figure 2B). [0018] Figs.3A-3C provide graphical representations of composite particles that have a combination of the energy converters (30) mixed with particles made of a high enough atomic mass material (32), wherein Fig.3A shows particles of the energy converter having low atomic mass (i.e. difficult to detect using X-ray imaging) (30) and particles of a high atomic mass material (i.e. readily detectible by X-ray imaging) (32) that have been sized and mixed using a ball-mill to provide a dispersed mixture; Fig.3B shows an encapsulation (34) by a polymer binder or resin around the particles of the energy converter (30) and high 5 6240479.1 atomic mass material (32); and Fig.3C shows the encapsulated composite particles having a coating (36) formed thereon. [0019] Fig.4 provides a graphical representation of a mixture of particles of an energy converter having low atomic mass with particles of a high atomic mass material, showing a plurality of energy converter particles (40) having a coating (42) such as a DLC coating, combined with particles of a high atomic mass material (44) which is preferably also coated with the coating (42), which may be the same coating or a different coating as that used on the energy converter particles (40). [0020] Fig.5A provides a graphical representation of an energy converter particle (50) having a coating (58) on the particle surface formed from a conventional imaging contrast agent. [0021] Fig.5B provides a graphical representation of one modification of the particles of Fig.5A, in which the energy converter particles (50) are first covered with a high transmissibility coating (52), preferably formed from a biologically compatible and inert material, before forming the coating (58) of the contrast agent. [0022] Fig.6 provides a graphical representation of the improvements in emissions and thus imaging using materials having a structure as depicted in Fig.3B, in the presence of the high atomic mass material. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS [0023] The present invention provides a variety of methods for enhancing the radioimaging of energy modulation agents, to better enable their detection within the body once administered, wherein the methods comprise: (_{i) coating a dried energy modulation agent with a coating having high} transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, wherein the coating comprises one or more contrast agents in an amount sufficient to enhance radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent, and the coated energy modulation agents produced thereby; or (_{ii) coating a dried energy modulation agent with a first coating having} high transmissibility at a wavelength of primary emission from the 6 6240479.1 energy modulation agent upon excitation, and applying a second coating on the first coating, wherein the second coating comprises one or more contrast agents, wherein the second coating enhances radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent; or (_{iii) forming a coating on a surface of particles of the energy modulation} agent, wherein the coating comprises one or more contrast agents; or (_{iv) forming a crystalline energy modulation agent having incorporated} therein an imageable amount of one or more high atomic mass dopants in a crystalline lattice of the crystalline energy modulation agent; or (_{v) mixing a first plurality of particles comprising one or more energy} modulation agents with a second plurality of particles comprising one or more high atomic mass materials to provide the energy modulation agent particle mixture having enhanced radioimageability; or (_{vi) providing a dispersed particle mixture comprising a first plurality of} particles of one or more energy modulation agents and a second plurality of particles of one or more high atomic mass materials; and mixing the dispersed particle mixture with a polymer binder to encapsulate one or more of the first plurality of particles and one or more of the second plurality of particles within the polymer binder, thus providing a plurality of energy converting composite particles each containing one or more energy modulation agents and one or more high atomic mass materials. [0024] The present invention relates to a method for enhancing radioimaging of a coated energy modulation agent, comprising: coating a dried energy modulation agent with a coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, wherein the coating comprises one or more submicron sized contrast agents in an amount sufficient to enhance radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent. [0025] The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. 7 6240479.1 As used in the description of the embodiments of the invention and the appended claims, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Also, as used herein, “and/or” refers to and encompasses any and all possible combinations of one or more of the associated listed items. Furthermore, the terms “at” or “about,” as used herein when referring to a measurable value or metric is meant to encompass variations of 20%, 10%, 5%, 1%, 0.5%, or even 0.1% of the specified amount, for example a specified ratio, a specified thickness, a specified phosphor size, or a specified water contact angle. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. [0026] Imaging techniques allow healthcare professionals to visualize the internal structures of mammalian bodies without invasive procedures, helping them make accurate diagnoses and treatment plans. There are a variety of commonly used imaging techniques in the medical field. Several of these include, but are not limited to, those listed below by way of example and illustration: [0027] X-ray Radiography: X-rays use ionizing radiation to create images of bones and dense tissues. They are commonly used to detect fractures, lung conditions, and dental issues. [0028] Computed Tomography (CT) Scan: CT scans use a series of X-ray images taken from different angles to create cross-sectional images of the body. They are used to visualize organs, soft tissues, and bones in detail. [0029] Magnetic Resonance Imaging (MRI): MRI uses strong magnetic fields and radio waves to create detailed images of the body's internal structures. It is particularly useful for imaging the brain, spinal cord, joints, and soft tissues. [0030] Ultrasound: Ultrasound uses high-frequency sound waves to create real-time images of organs and tissues. It is commonly used during pregnancy to monitor fetal development and for imaging the abdomen, heart, and blood vessels. [0031] Positron Emission Tomography (PET): PET scans involve the injection of a small amount of radioactive material into the body. It is used to detect metabolic activity and is valuable for cancer staging and neurological studies. [0032] Single Photon Emission Computer Tomography (SPECT): SPECT is a nuclear imaging technique that uses a radioactive tracer to create 3D images of organ function. It is often used in cardiology and neurology. 8 6240479.1 [0033] Mammography: Mammography is a specialized X-ray technique used for breast cancer screening and diagnosis. Digital mammography and 3D mammography (tomosynthesis) are modern variations. [0034] Fluoroscopy: Fluoroscopy is a real-time X-ray technique used to visualize moving structures like the gastrointestinal tract during procedures like barium enemas and cardiac catheterizations. [0035] Endoscopy: Endoscopy involves the use of a flexible tube with a camera at the end to visualize the inside of organs and cavities, such as the gastrointestinal tract, respiratory tract, and joints. [0036] Angiography: Angiography is a technique that uses contrast dye and X-rays to visualize blood vessels, helping diagnose vascular conditions like aneurysms or blockages. [0037] Nuclear Medicine Imaging: This category includes various imaging techniques like bone scans, thyroid scans, and myocardial perfusion scans that use radioactive tracers to assess organ function. [0038] Intravascular Ultrasound (IVUS): IVUS is a specialized ultrasound technique used during catheter-based procedures to visualize blood vessels from within, providing high- resolution images of vessel walls. [0039] Functional MRI (fMRI): fMRI is an advanced MRI technique that measures brain activity by detecting changes in blood flow. It is widely used in neuroscience and neurology. [0040] Diffusion-Weighted Imaging (DWI): DWI is an MRI technique that measures the movement of water molecules in tissues and is particularly useful for detecting stroke and some types of cancer. [0041] Elastography: Elastography is a specialized ultrasound technique that assesses tissue stiffness and is valuable for liver fibrosis evaluation and breast lesion characterization. Imaging techniques play a crucial role in the diagnosis and management of a wide range of medical conditions, from trauma and cancer to neurological disorders and cardiovascular diseases. [0042] Advances in imaging technology continue to improve the accuracy and safety of medical diagnoses and treatments. [0043] The present invention addresses advances in imaging to enable the direct or indirect visualization of energy converters used to convert a deeply penetrating energy into a UV energy without line of sight. A direct imaging technique is akin to an X-ray imaging technique. An indirect imaging technique is similar to a computer assisted reconstruction of an image used in ultrasound imaging. 9 6240479.1 [0044] Examples of conventional X-ray based imaging equipment providers include, but are not limited to: Siemens offers a wide range of X-ray imaging equipment, including digital radiography systems, fluoroscopy systems, and mobile X-ray systems. Their products are used for various medical applications, from routine diagnostic imaging to specialized procedures. GE Healthcare manufactures X-ray systems that include digital radiography systems, mobile X-ray systems, and fluoroscopy systems. They provide a range of solutions designed to meet the diverse imaging needs of healthcare facilities. Philips produces a variety of X-ray systems, such as digital radiography systems, fluoroscopy systems, and mobile X- ray systems. Their products are designed to offer high-quality imaging for different clinical applications. Canon Medical Systems offers a range of X-ray solutions, including digital radiography systems, mobile X-ray systems, and fluoroscopy systems. Their products are designed to provide efficient and high-quality imaging for various medical procedures. Carestream Medical Systems provides digital radiography systems, computed radiography systems, and other X-ray imaging solutions. They offer a range of products tailored to meet the imaging needs of healthcare providers. [0045] Energy Modulation Agent [0046] As used herein, an “energy modulation agent” refers to an agent that is capable of receiving an energy input from a source and then re-emitting a different energy to a receiving target. Energy transfer among molecules may occur in a number of ways. The form of energy may be electronic, thermal, vibronic, electromagnetic, kinetic, or chemical in nature. Energy may be transferred from one molecule to another (intermolecular transfer) or from one part of a molecule to another part of the same molecule (intramolecular transfer). For example, a modulation agent may receive electromagnetic energy and re-emit energy in the form of thermal energy or energy which otherwise contributes to heating the environment in vicinity of the light emission. Within the present application, the terms “energy modulation agent” and “energy converter” are used interchangeably. [0047] In various embodiments, the energy modulation agent (down converters, mixtures of down converters, up converters, mixtures of up converters, and combinations thereof) receives energy from a source and re-emits the energy (e.g. UV-A and/or visible light). Some energy modulation agents may have a very short energy retention time (on the order of femtoseconds (fs), e.g. fluorescent molecules) whereas others may have a very long half-life (on the order of minutes to hours, e.g. luminescent or phosphorescent molecules). Suitable energy modulation agents include, but are not limited to, a biocompatible fluorescing metal nanoparticle, fluorescing dye molecules, gold nanoparticle, a quantum dot, a quantum dot 10 6240479.1 encapsulated by polyamidoamine dendrimers, a luciferase, a biocompatible phosphorescent molecule, a combined electromagnetic energy harvester molecule, and a lanthanide chelate capable of intense luminescence. These energy modulation agents (some of which are described above as nanoparticles) need not be of nanometer size and can in various embodiments of this invention be of micron-sized proportions. Typically, the energy modulation agents (down converters, mixtures of down converters, up converters, mixtures of up converters, and combinations thereof) induce photoreactive changes in the medium and are not used for the purpose of exclusively heating the medium. [0048] In the present invention, energy converters can be generally placed into two broad categories: high atomic mass and low atomic mass energy converting materials. All the upconverting and down-converting materials that have high atomic mass can be imaged using X-ray energy. Conversely, all upconverting and down converting materials that have a low atomic mass cannot easily be imaged using standard X-Ray imaging. These low atomic mass materials can still be imaged using other techniques that are not based on the interaction of an X-ray photon with the atomic constituents. For example, acoustic based imaging or MRI can still be used to image these low atomic mass materials. However, because of the higher prevalence, availability, and portability of X-ray imaging equipment, it is advantageous to be able to image these materials during X-Ray, such as, for example, by using the on-board imaging in a LINAC machine used to activate these materials. [0049] X-rays interact with matter though the processes of photoelectric absorption, Compton scattering and coherent scattering. The ability of an element to interact with X-rays depends on several factors, including the element’s atomic number (Z) and electron density. Generally, elements with higher atomic mass or higher atomic number and greater electron densities are more likely to interact with X-rays. Elements with higher atomic numbers (typically above 20) are considered heavy enough to strongly interact with X-rays. These materials include, but are not limited to, Iron (Z=26), Copper (Z=29), Silver (Z=47) Iodine (Z=53), Barium (Z=56), Gold (Z=79), Lead (Z=82). On the other hand, atomic numbers and lower electron densities are less strongly coupling to X-rays. These include elements below oxygen (Z=8). [0050] For these reasons described above, methods that impart a high enough atomic mass that can be imageable using X-ray are of interest. These methods can be categorized in five (5) main categories: 1- energy converters containing added atomic dopants in the crystalline lattice; 2- energy converting particles having an added coating on their surface that contains a high atomic mass material doped therein; 3- composite particles that have a combination of 11 6240479.1 the energy converters mixed with particles made of a high enough atomic mass material; 4- mixtures of particles containing particles of a high atomic mass material mixed with energy converting particles of low atomic mass; and 5- energy converting particles having low atomic mass that are coated with a dried contrast agent. In the 4^th category, both the particles that can be imaged and the energy converters can be coated with a diamond-like carbon (DLC) coating to ensure the same surface chemistry. DLC coatings are discussed further below. [0051] Within the context of the present invention, the energy modulation agent is preferably in the form of a particulate, more preferably in the form of a powder, for ease of coating the particles of the energy modulation agent. [0052] Other suitable energy modulation agents include organic fluorescent molecules or inorganic particles capable of fluorescence and/or phosphorescence having crystalline, polycrystalline or amorphous micro-structures. [0053] It is worth highlighting that crystallinity has different subcategories that are highlighted here for clarification. Crystalline materials have long range order, and such is the case of single crystalline and polycrystalline materials. These materials have a predominantly repetitive lattice that is found in the material at any scale. On the other hand, there are materials that exhibit a short-term (limited scale) order but no long-term order. These materials are exemplified in silicate structures that are crystalline below 50 Angstroms but that are amorphous at bigger scales above 100 Angstroms. For illustration, a relevant example in this case is silicate-based phosphors that can be doped for better imaging. The introduction of calcium (Ca) instead of potassium (K) or lithium (Li) in silicate phosphors increases the likelihood of imaging using X-rays. Though Ca is a divalent ion and K and Li are monovalent ions, Ca can enter the interstitial place between silica tetrahedra to satisfy charge neutrality between two non-bridging oxygens. One calcium can therefore substitute two potassium ions or two lithium ions. Furthermore, introducing zinc oxide in the silicate chemistry increases the crystallinity (longer range order) and also has a positive impact on imaging. [0054] Organic fluorescent compounds with high quantum yield include, but are not limited to, naphthalene, pyrene, perylene, anthracene, phenanthrene, p-terphenyl, p-quaterphenyl, trans-stilbene, tetraphenylbutadiene, distyrylbenzene, 2,5-diphenyloxazole, 4-methyl-7- diethylaminocoumarin, 2-phenyl-5-(4-biphenyl)-1,3,4-oxadiazole, 3-phenylcarbostyryl, 1,3,5-triphenyl-2-pyrazoline, 1,8-naphthoylene -1’, 2’-benzimidazole, 4-amino-n-phenyl- naphthalimide. 12 6240479.1 [0055] Inorganic fluorescent and/or phosphorescent materials span a wide variety of materials. Furthermore, these materials can be doped with specific ions (activators or a combination of activators) that occupy a site in the lattice structure in the case of crystalline or polycrystalline materials and could occupy a network forming site or a bridging and/or non-bridging site in amorphous materials. These compounds include, but are not limited to, (not ranked by order of preference or utility): CaF₂, ZnF₂, KMgF₃, ZnGa₂O₄, ZnAl₂O₄, Zn₂SiO₄, Zn₂GeO₄, Ca₅(PO₄)₃F, Sr₅(PO₄)₃F, CaSiO₃, MgSiO₃, ZnS, MgGa₂O₄, LaAl₁₁O₁₈, Zn₂SiO₄, Ca₅(PO₄)₃F, Mg₄Ta₂O₉, CaF₂, LiAl₅O₈, LiAlO₂, CaPO₃, AlF₃, and LuPO₄:Pr³⁺. Examples further include the alkali earth chalcogenide phosphors which are in turn exemplified by the following non-inclusive list: MgS:Eu³⁺, CaS:Mn²⁺, CaS:Cu, CaS:Sb, CaS:Ce³⁺, CaS:Eu²⁺, CaS:Eu²⁺Ce³⁺, CaS:Sm³⁺, CaS:Pb²⁺, CaO:Mn²⁺, CaO:Pb²⁺, Ca₃(PO₄)₂:Tl⁺, (Ca, Zn)₃(PO₄)₂:Tl⁺. [0056] Further examples include the ZnS type phosphors that encompass various derivatives: ZnS:Cu,Al(Cl), ZnS:Cl(Al), ZnS:Cu,I(Cl), ZnS:Cu, ZnS:Cu,In. [0057] Also included are the compound IIIb-Vb phosphors which include the group IIIb and Vb elements of the periodic table. These semiconductors include BN, BP, BSb, AlN, AlP, AlAs, AlSb, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb and these materials may include donors and acceptors that work together to induce light emission diodes. These donors include, but are not limited to, Li, Sn, Si, Li, Te, Se, S, O and acceptors include, but are not limited to, C, Be, Mg, Zn, Cd, Si, Ge. Further included are the major GaP light emitting diodes which include, but are not limited to, GaP:Zn,O, GaP:NN, Gap:N and GaP, which emit colors Red, Yellow, Green and Pure Green respectively. [0058] The energy modulation agents can further include such materials as GaAs with compositional variation of the following sort: In_1-y(Ga_1-xAl_x)_yP. [0059] Also included is silicon carbide SiC, which has commercial relevancy as a luminescent platform in blue light emitting diodes. These include the polytypes 3C-SiC, 6H- SiC, 4H-SiC with donors such as N and Al and acceptors such as Ga and B. [0060] Further examples include multiband luminescent materials include, but not limited to, the following compositions (Sr, Ca, Ba)5(PO4)3Cl:Eu²⁺, BaMg2Al16O27:Eu²⁺, CeMgAl11O19:Ce³⁺:Tb³⁺, LaPO4:Ce³⁺:Tb³⁺, GdMgB5O10:Ce3:Tb³⁺, Y2O3:Eu³⁺, (Ba,Ca,Mg)5(PO4)3Cl:Eu²⁺, 2SrO0.84P2O50.16B2O3:Eu²⁺, Sr4Al14O25:Eu²⁺. [0061] Materials typically used for fluorescent high pressure mercury discharge lamps are also included. These can be excited with X-Ray and are exemplified by way of family designation as follows: Phosphates (Sr, M)(PO4)2:Sn²⁺, Mg or Zn activator, Germanate 13 6240479.1 4MgO.GeO₂:Mn⁴⁺, 4(MgO, MgF₂)GeO₂:Mn⁴⁺, Yttrate Y₂O₃:Eu³⁺, Vanadate YVO₄:Eu³⁺, Y(P,V)O4:Eu³⁺, Y(P,V)O4:In⁺, Halo-Silicate Sr2Si3O82SrCl2:Eu²⁺, Aluminate (Ba,Mg)₂Al₁₆O₂₄:Eu²⁺, (Ba, Mg)₂Al₁₆O₂₄:Eu²⁺,Mn²⁺, Y₂O₃Al₂O₃:Tb³⁺. [0062] Another grouping by host compound includes chemical compositions in the halophosphates phosphors, phosphate phosphors, silicate phosphors, aluminate phosphors, borate phosphors, tungstate phosphors, and other phosphors. The halophosphates include, but are not limited to: 3Ca₃(PO₄)₂.Ca(F,Cl)₂:Sb³⁺, 3Ca₃(PO₄)₂.Ca(F,Cl)₂:Sb³⁺/Mn²⁺, Sr₁₀(PO₄)₆Cl₂:Eu²⁺, (Sr,Ca)₁₀(PO₄)₆Cl₂:Eu²⁺, (Sr,Ca)₁₀(PO₄)₆.nB₂O₃:Eu³⁺, (Sr, Ca,Mg)10(PO4)6Cl2:Eu²⁺. The phosphate phosphors include, but are not limited to: Sr₂P₂O₇:Sn²⁺, (Sr,Mg)₃(PO₄)₂:Sn²⁺, Ca₃(PO₄)₂.Sn²⁺, Ca₃(PO₄)₂:Tl⁺, (Ca,Zn)₃(PO₄)₂:Tl⁺, Sr2P2O7:Eu²⁺, SrMgP2O7:Eu²⁺, Sr3(PO4)2:Eu²⁺, LaPO4:Ce³⁺, Tb³⁺, La₂O₃.0.2SiO₂.0.9P₂O₅:Ce³⁺.Tb³⁺, BaO.TiO₂.P₂O₅. The silicate phosphors Zn₂SiO₄:Mn²⁺, CaSiO3:Pb²⁺/Mn²⁺, (Ba, Sr, Mg).3Si2O7:Pb²⁺, BaSi2O5:Pb²⁺, Sr2Si3O8.2SrCl2:Eu²⁺, Ba₃MgSi₂O₈:Eu²⁺, (Sr,Ba)Al₂Si₂O₈:Eu²⁺. [0063] The aluminate phosphors include, but are not limited to: LiAlO2:Fe³⁺, BaAl₈O₁₃:Eu²⁺, BaMg₂Al₁₆O₂₇:Eu²⁺, BaMg₂Al₁₆O₂₇:Eu²⁺/Mn²⁺, Sr₄Al₁₄O₂₅:Eu²⁺, CeMgAl11O19:Ce³⁺/Tb³⁺. [0064] The borate phosphors include: Cd₂B₂O₅:Mn²⁺, SrB₄O₇F:Eu²⁺, GdMgB₅O₁₀:Ce³⁺/Tb³⁺, GdMgB5O10:Ce³⁺/Mn³⁺, GdMgB5O10:Ce³⁺/Tb³⁺/Mn²⁺. [0065] The tungstate phosphors include, but are not limited to: CaWO₄, (Ca,Pb)WO₄, MgWO4. Other phosphors Y2O3:Eu³⁺, Y(V,P)O4:Eu²⁺, YVO4:Dy³⁺, MgGa2O4:Mn²⁺, 6MgO.As₂O₅:Mn²⁺, 3.5MgO.0.5MgF₂.GeO₂:Mn⁴⁺. [0066] The activators to the various doped phosphors include, but are not limited to: Tl⁺, Pb²⁺, Ce³⁺, Eu²⁺, WO₄ ^2-, Sn²⁺, Sb³⁺, Mn²⁺, Tb³⁺, Eu³⁺, Mn⁴⁺, Fe³⁺. The luminescence center Tl⁺ is used with a chemical composition such as: (Ca,Zn)3(PO4)2:Tl⁺, Ca3(PO4)2:Tl⁺. The luminescence center Mn²⁺ is used with chemical compositions such as MgGa₂O₄:Mn²⁺, BaMg2Al16O27:Eu²⁺/Mn²⁺, Zn2SiO4:Mn²⁺, 3Ca3(PO4)2.Ca(F,Cl)2:Sb²⁺/Mn²⁺, CaSiO3:Pb²⁺/Mn²⁺, Cd2B2O5:Mn²⁺, CdB2O5:Mn²⁺, GdMgB5O10:Ce³⁺/Mn²⁺, GdMgB5O10:Ce³⁺/Tb³⁺/Mn²⁺. The luminescence center Sn2+ is used with chemical compositions such as: Sr2P2O7:Sn²⁺, (Sr,Mg)3(PO4)2:Sn²⁺. The luminescence center Eu²⁺ is used with chemical compositions such as: SrB4O7F:Eu²⁺, (Sr,Ba)Al2Si2O8:Eu²⁺, Sr3(PO4)2:Eu²⁺, Sr2P2O7:Eu²⁺, Ba3MgSi2O8:Eu²⁺, Sr10(PO4)6Cl2:Eu²⁺, BaMg2Al16O27:Eu²⁺/Mn²⁺, (Sr,Ca)10(PO4)6Cl2:Eu²⁺. The luminescence center Pb²⁺ is used 14 6240479.1 with chemical compositions such as: (Ba,Mg,Zn)₃Si₂O₇:Pb²⁺, BaSi₂O₅:Pb²⁺, (Ba,Sr)3Si2O7:Pb²⁺. [0067] The luminescence center Sb²⁺ is used with chemical compositions such as: 3Ca3(PO4)2.Ca(F,Cl)2:Sb³⁺, 3Ca3(PO4)2.Ca(F,Cl)2:Sb³⁺/Mn²⁺. [0068] The luminescence center Tb³⁺ is used with chemical compositions such as: CeMgAl₁₁O₁₉:Ce³⁺/Tb³⁺, LaPO₄:Ce³⁺/Tb³⁺, Y₂SiO₅:Ce³⁺/Tb³⁺, GdMgB₅O₁₀:Ce³⁺/Tb³⁺. The luminescence center Eu³⁺ is used with chemical compositions such as: Y₂O₃:Eu³⁺, Y(V,P)O₄:Eu³⁺. The luminescence center Dy³⁺ is used with chemical compositions such as: YVO4:Dy³⁺. The luminescence center Fe³⁺ is used with chemical compositions such as: LiAlO₂:Fe³⁺. The luminescence center Mn⁴⁺ is used with chemical compositions such as: 6MgO.As2O5:Mn⁴⁺, 3.5MgO0.5MgF2.GeO2:Mn⁴⁺. The luminescence center Ce³⁺ is used with chemical compositions such as: Ca₂MgSi₂O₇:Ce³⁺ and Y₂SiO₅:Ce³⁺. The luminescence center WO4^2- is used with chemical compositions such as: CaWO4, (Ca,Pb)WO4, MgWO4. The luminescence center TiO₄ ^4- is used with chemical compositions such as: BaO.TiO₂.P₂O₅. [0069] Additional phosphor chemistries of interest using X-Ray excitations include, but are not limited to, the k-edge of these phosphors. Low energy excitation can lead to intense luminescence in materials with low k-edge. Some of these chemistries and the corresponding k-edge are listed below: BaFCl:Eu²⁺ 37.38 keV BaSO₄:Eu²⁺ 37.38 keV CaWO4 69.48 keV Gd₂O₂S:Tb³⁺ 50.22 keV LaOBr:Tb³⁺ 38.92 keV LaOBr:Tm³⁺ 38.92 keV La2O2S:Tb³⁺ 38.92 keV Y₂O₂S:Tb³⁺ 17.04 keV YTaO4 67.42 keV YTaO4:Nb 67.42 keV ZnS:Ag 9.66 keV (Zn,Cd)S:Ag 9.66/26.7 keV [0070] These materials can be used alone or in combinations of two or more. A variety of compositions can be prepared to obtain the desired output wavelength or spectrum of wavelengths. 15 6240479.1 [0071] These energy modulation agents can be used in a wide variety of applications, including but not limited to, medical treatments using energy generated in vivo within a subject being treated, solar cells, adhesives and other resins, sterilization treatment for various materials (such as wastewater, beverages, etc). The use of energy modulation agents in such applications has been described in the following: US Published Application No. 2008/0248001; US Published Application No.2009/0104212; US Published Application No. 2009/0294692; US Published Application No.2010/0003316; US Published Application No. 2010/0016783; US Published Application No.2010/0261263; US Published Application No. 2010/0266621; US Published Application No.2011/0021970; US Published Application No. 2011/0117202; US Published Application No.2011/0126889; US Published Application No. 2011/0129537; US Published Application No.2011/0263920; US Published Application No. 2012/0064134; US Published Application No.2012/0089180; US Published Application No. 2013/0102054; US Published Application No.2013/0129757; US Published Application No. 2013/0131429; US Published Application No.2013/0156905; US Published Application No. 2013/0171060; US Published Application No.2013/0240758; US Published Application No. 2014/0134307; US Published Application No.2014/0163303; US Published Application No. 2014/0166202; US Published Application No.2014/0222117; US Published Application No. 2014/0242035; US Published Application No.2014/0243934; US Published Application No. 2014/0272030; US Published Application No.2014/0323946; US Published Application No. 2014/0341845; US Published Application No.2014/0343479; US Published Application No. 2015/0182934; US Published Application No.2015/0202294; US Published Application No. 2015/0246521; US Published Application No.2015/0251016; US Published Application No. 2015/0265706; US Published Application No.2015/0283392; US Published Application No. 2015/0290614; US Published Application No.2016/0005503; US Published Application No. 2016/0067524; US Published Application No.2016/0159065; US Published Application No. 2016/0243235; US Published Application No.2016/0263393; US Published Application No. 2016/0325111; US Published Application No.2016/0331731; US Published Application No. 2016/0354467; US Published Application No.2016/0362534; US Published Application No. 2017/0027197; US Published Application No.2017/0043178; US Published Application No. 2017/0050046; US Published Application No.2017/0096585; US Published Application No. 2017/0113061; US Published Application No.2017/0121472; US Published Application No. 2017/0154866; US Published Application No.2017/0157418; US Published Application No. 2017/0162537; US Published Application No.2017/0173350; US Published Application No. 2017/0186720; US Published Application No.2017/0190166; US Published Application No. 16 6240479.1 2017/0196977; US Published Application No.2017/0239489; US Published Application No. 2017/0239637; US Published Application No.2017/0240717; US Published Application No. 2017/0258908; US Published Application No.2017/0319868; US Published Application No. 2017/0319869; US Published Application No.2018/0036408; US Published Application No. 2018/0154171; US Published Application No.2018/0154178; US Published Application No. 2018/0169433; US Published Application No.2018/0170028; US Published Application No. 2018/0269174; US Published Application No.2018/0271121; US Published Application No. 2018/0304225; US Published Application No.2018/0311355; US Published Application No. 2018/0317307; US Published Application No.2018/0344850; US Published Application No. 2018/0358327; US Published Application No.2019/0016869; US Published Application No. 2019/0022221; US Published Application No.2019/0100680; US Published Application No. 2019/0134419; US Published Application No.2019/0134595; US Published Application No. 2019/0134596; US Published Application No.2019/0157234; US Published Application No. 2019/0168015; US Published Application No.2019/0184190; US Published Application No. 2019/308030; US Published Application No.2019/0336605; US Published Application No. 2019/0336785; US Published Application No.2019/0336786; US Published Application No. 2019/0341364; US Published Application No.2020/0009398; US Published Application No. 2020/0078600; US Published Application No.2020/0079926; US Published Application No. 2020/0114164; US Published Application No.2020/0196639; US Published Application No. 2020/0215611; US Published Application No.2020/0222711; US Published Application No. 2020/0282056; US Published Application No.2020/0306717; US Published Application No. 2020/0323711; US Published Application No.2020/0365552; US Published Application No. 2020/0368547; US Published Application No.2021/0035946; US Published Application No. 2021/0145028; US Published Application No.2021/0253954; US Published Application No. 2022/0062419; US Published Application No.2022/0080045; US Published Application No. 2022/0134131; US Published Application No.2022/0146076; US Published Application No. 2022/0148997; US Published Application No.2022/0159998; US Published Application No. 2022/0181292; US Published Application No.2022/0184211; US Published Application No. 2022/0193441; US Published Application No.2022/0226666; the contents of each of which are hereby incorporated by reference in their entireties. [0072] The Present Invention Method [0073] In one embodiment, the present invention relates to a method for enhancing radioimaging of a coated energy modulation agent, comprising: 17 6240479.1 coating a dried energy modulation agent with a coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, wherein the coating comprises one or more submicron sized contrast agents in an amount sufficient to enhance radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent. [0074] The coating can be any desired coating for the energy modulation agent, preferably one that is inert in relation to the end use intended for the energy modulation agent. For example, for medical use, the coating is preferably a biocompatible coating, in order to protect the subject being treated, as well as avoid migration of any of the energy modulation agent composition into the patient’s system. The coating can be made from a variety of materials, so long as the coating has the ability to transmit the emission wavelength(s) of the energy modulation agent being coated when the energy modulation agent is activated by an applied energy (i.e. high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation). Various optically transparent coatings are known, such as coatings formed from: inorganic materials, including, but not limited to, silica, phosphate, and silicon oxynitride; natural materials, including, but not limited to, silk, cellulose, and bacterial cells; hydrogels, including, but not limited to, agarose gel, polyethylene glycol (PEG) and derivatives thereof, and alginate; synthetic polymers, including, but not limited to, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), and poly(lactic-co-glycolic acid) (PLGA); elastomers, including, but not limited to, polydimethylsiloxane (PDMS) and poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC); and multifunctional hybrid materials, including, but not limited to, cyclic olefin copolymer (COC), polycarbonate (PC), and conductive polyethylene (CPE). (for further details on these materials and optical properties see Nazempour, R, et al, Materials (Basel).2018 Aug; 11(8): 1283, the entire contents of which are hereby incorporated by reference). Other options for the high transmissibility coating include a biocompatible layer- by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA). (see Ermatov, T. et al, Optics Letters, Vol.46, Issue 19, pp.4828-4831 (2021), the entire contents of which are hereby incorporated by reference). Other possible coatings include optical coatings offered commercially by Evaporated Coatings, Inc (www.evaporatedcoatings.com). Still further high transmissibility coatings include coatings formed from deposition of methyltriethoxysilane/trimethoxymethylsilane. (see Mahadik, S. A., J Sol-Gel Sci Technol (2017) 81:791–796, the entire contents of which are hereby incorporated by reference). Most 18 6240479.1 preferably, the coating is a diamond or diamond-like carbon (DLC) coating. Along with any of the above coatings, the energy modulation agent may be optionally first coated with a biocompatible ethyl cellulose coating prior to the coating having high transmissibility. [0075] In one embodiment of the invention, the energy modulation agent particles are first coated with a biocompatible Ethyl Cellulose coating, and then overcoated with a second coating of Diamond Like Carbon (DLC). [0076] Ethyl Cellulose (EC) is widely used in biomedical applications today, including artificial kidney membranes, coating materials for drugs, blood coagulants, additives of pharmaceutical products, blood compatible materials. EC and its derivatives have been widely used in various, personal care, food, biomedical and drug related applications. EC is not a skin sensitizer, it is not an irritant to the skin, and it is not mutagenic. EC is generally regarded as safe (GRAS), and widely used for example in food applications such flavor encapsulation, inks for making fruits and vegetables, paper and paperboard in contact with aqueous and fatty foods. [0077] EC is also widely used for controlled release of active ingredients. The enhanced lipophilic and hydrophobic properties make it a material of choice for water resistant applications. EC is soluble in various organic solvents and can form a film on surfaces and around particles (such as phosphors). In one embodiment of this invention, ethyl cellulose is used to encapsulate the energy modulation agent particles to ensure that an added degree of protection is in place on the surface of the energy modulation agent particles. The particles are then preferably coated with a further coating of diamond or diamond-like carbon (DLC). In one embodiment of this invention, EC polymers with high molecular weight for permanent encapsulation and long term biocompatibility are used to encapsulate the energy modulation agent particles. In a preferred embodiment, the EC polymer can be any commercially available pharmaceutical grade ethyl cellulose polymer having sufficient molecular weight to form a coating on the energy modulation agent surface. Suitable EC polymers include, but are not limited to, the ETHOCEL brand of ethyl cellulose polymers available from Dow Chemical, preferably ETHOCEL FP grade products, most preferably ETHOCEL FP 100. [0078] Diamond Like Carbon (DLC) films are in general dense, mechanically hard, smooth, impervious, abrasion resistant, chemically inert, and resistant to attack by both acids and bases; they have a low coefficient of friction, low wear rate, are biocompatible and thromboresistant. Tissues adhere well to carbon coated implants and sustain a durable interface. In presence of blood, a protein layer is formed which prevents the formation of 19 6240479.1 blood clots at the carbon surface. For medical prostheses that contact blood (heart valves, anathomic sheets, stents, blood vessels, etc.), DLC coatings have been used. [0079] DLC has emerged over the past decade as a versatile and useful biomaterial. It is harder than most ceramics, bio-inert, and has a low friction coefficient. DLC is one of the best materials for implantable applications. Studies of the biocompatibility of DLC demonstrate that there is no cytotoxicity and cell growth is normal on a DLC-coated surface. (DLC coatings on stainless steel have performed very well in in vitro studies of hemocompatibility. Histopathological investigations have shown good biotolerance of implants coated with the DLC. Moreover, DLC as a coating is efficient protection against corrosion. These properties make the embodiment described here with a double coating (EC and DLC) particularly advantageous for the energy modulation agent particles. [0080] Methods for coating the energy modulation agents with EC or DLC are known to those of ordinary skill, and have been described, for example, in PCT/US2015/027058 filed April 22, 2015, incorporated earlier by reference. [0081] In one embodiment of the invention, the diamond or DLC coating is coated onto the energy modulation agent by Physical Vapor Deposition to encapsulate the energy modulation agent and to further enhance their biocompatibility. [0082] For the DLC film, a preferred thickness is 60 to 115 nm, more preferably 60 to 90 nm, most preferably 70 nm +/- 5 nm. [0083] In certain embodiments, the energy modulation agent can be first dried prior to application of the first coating. In embodiments, the drying can be carried out in any desired manner, including, but not limited to, drying at a temperature and/or pressure sufficient to reduce the moisture content by a desired amount, or removing the moisture (or resident water) via a simple solvent exchange, such as by soaking the raw undried phosphors in one of a variety of solvents that are miscible with water, but have significantly higher vapor pressures, lower boiling points, or both. [0084] In such a solvent exchange process, phosphors are washed in a solvent, such as one of the semi-polar alcohols (for example, methanol, ethanol, isopropanol, etc.), whereby the residual water gets replaced within the phosphor by the solvent, prior to the coating process without the need for heat or vacuum drying. Alternatively, the vapor pressure of the resident solvent (such as alcohol) then resident on the phosphor would allow more efficient and facile removal of the binary water-solvent admixture resulting in the need for lower temp, time and reduced pressure. 20 6240479.1 [0085] In drying the phosphors without the use of such solvent exchange (or even with such use of solvent exchange), the time, temperature, and pressure for drying the energy modulation are chosen such that the moisture content of the energy modulation agent is reduced during drying by at least 25wt%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 90%, at least 95%, at least 98%, or at least 99%. [0086] In one embodiment of the present invention, the drying is performed at a temperature of from 60°C to 200°C, preferably from 90°C to 150°C, more preferably from 100°C to 130°C, still more preferably from 120°C to 130°C, most preferably at a temperature of 125°C +/- 2°C. [0087] In a further embodiment of the present invention, the pressure of drying can be any desired pressure, preferably from atmospheric pressure (760 mm Hg abs) to <1 mm Hg abs (high vacuum), more preferably from atmospheric pressure (760 mm Hg abs) to 680 mm Hg abs (low vacuum). [0088] The drying is performed for any time period depending on the choice of temperature and pressure, and is preferably from 1 hour to 21 days, more preferably from 1-21 days, still more preferably from 3-15 days, most preferably for 10-15 days. [0089] In certain embodiments of the present invention method the coating is applied to a thickness of 60 nm to 115 nm, more preferably 60 to 90 nm, most preferably 70 nm +/- 5 nm. This is particularly the case for the preferred embodiment of using a DLC coating. [0090] In certain preferred embodiments of the present invention, the drying is performed at a temperature from 90°C to 150°C at a pressure from atmospheric pressure (760 mm Hg abs) to 650 mm Hg abs for a period of time from 1-21 days. In further preferred embodiments of the present invention, the drying is performed at a temperature of 100°C to 130°C at a pressure from atmospheric pressure (760 mm Hg abs) to 680 mm Hg abs for a period of time from 3-15 days. [0091] In the present invention method, the energy modulation agent can be a single compound or a mixture of two or more energy modulation agents, selected to provide desired predominant emission wavelengths. The energy modulation agent can be any of those energy modulation agents noted above, and in certain preferred embodiments, is a combination of two or more energy modulation agents. [0092] In one preferred embodiment, the energy modulation agent in the present method is an admixture of Zn2SiO4:Mn²⁺ and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of of from 1:10 to 10:1, or from 1:5 to 5:1, or from 1:2

in dry solid/powder form. 21 6240479.1 [0093] In embodiments of the method of the present invention, the high transmissibility coating contains one or more submicron sized contrast agents selected to increase the radioimaging characteristics of the energy modulation agent itself. In certain embodiments, these one or more submicron sized contrast agents are nanoparticles or other nanoscale structures (such as nanocapsules) that are sufficiently sized to be contained within the high transmissibility coating layer itself. [0094] The one or more submicron sized contrast agents can be any desired agent capable of radioimaging. Suitable submicron sized contrast agents include, but are not limited to, metal nanoparticles, lanthanide compound nanoparticles, metallic compound nanoparticles, polymeric nanoparticles, polymeric nanocapsules, and combinations thereof. [0095] In certain embodiments, the submicron sized contrast agents include, but are not limited to, gold-based nanoparticles, copper-based nanoparticles, tantalum-based nanoparticles, bismuth-based nanoparticles, iron-based nanoparticles, platinum-based nanoparticles, barium-based nanoparticles, lead-based nanoparticles, uranium-based nanoparticles, silver-based nanoparticles, and combinations, compounds, and alloys thereof. Such metal-based nanoparticles include not only the metal nanoparticles themselves, but also nanoparticles formed from compounds containing the recited metal, alloys of the recited metal with one or more other metals, and combinations of these metals, compounds or alloys. [0096] In certain embodiments, the submicron sized contrast agents include lanthanide compound nanoparticles, including, but not limited to, gadolinium compounds, dysprosium compounds, ytterbium compounds, europium compounds, terbium compounds, yttrium compounds, or combinations thereof. [0097] Various examples of such contrast agents are set forth in Lusic, H. et al, Chem Rev. 2013 March 13; 113(3): doi:10.1021/cr200358s; and in Aslan, N. et al, Journal of Molecular Structure 1219 (2020) 128599: doi.org/10.1016/j.molstruc.2020.128599, the entire contents of each of which are hereby incorporated by reference. [0098] In other embodiments of the present invention, the present invention provides a method for enhancing radioimaging of a coated energy modulation agent, comprising: coating a dried energy modulation agent with a first coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, and applying a second coating on the first coating, wherein the second coating comprises a member selected from the group consisting of liposomal contrast agents, contrast agent 22 6240479.1 containing nanoemulsions, contrast agent containing nanosuspensions, contrast agent containing nanocapsules, and combinations thereof, wherein the second coating enhances radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent. [0099] In these embodiments, the same type of contrast agents can be used as noted above, but in the form of the recited liposomes, nanoemulsions, nanosuspensions, nanocapsules, etc. The high transmissibility coatings in these embodiments can also be the same ones as noted above, with similar thicknesses, and with the same one or more energy modulation agents. [00100] In certain embodiments of the present invention, the invention relates to the coated energy modulation agents produced by the methods and having enhanced radioimaging capabilities. This enhanced radioimaging capability provides the ability, for example, to ensure more uniform distribution of the energy modulation agents throughout a tumor undergoing treatment, or throughout an adhesive layer for more uniform curing. By irradiating the medium (such as the tumor or adhesive layer in the examples recited above) containing the coated energy modulation agents of the invention, using an energy suitable for radioimaging with the selected contrast agent (such as x-rays), the location of the coated energy modulation agents can be more accurately identified within the medium to ensure more consistent production of energy emissions within the medium. [00101] The methods for enhanced imaging described above are further illustrated below, with reference to several Figures providing illustrative graphical representations. [00102] Doping in crystalline materials refers to the intentional introduction of impurity atoms or foreign elements into the crystal lattice of a material to alter its electrical, optical, or structural properties. Doping is a key process in the semiconductor industry and is crucial for the development of various electronic and optoelectronic devices. It allows for the manipulation of the conductivity and other characteristics of the material, enabling the creation of customized materials with specific properties tailored for different applications. Doping is a critical process in the fabrication of various semiconductor devices, including diodes, transistors, and integrated circuits. By carefully controlling the type and concentration of dopants, engineers and researchers can tailor the electrical and optical properties of semiconductor materials to meet specific requirements for electronic components and devices. This precise control over material properties has enabled the development of advanced technologies in fields such as microelectronics, photonics, and renewable energy. 23 6240479.1 [00103] As noted above, a first category of method that can impart a high enough atomic mass to make energy converters imageable using X-ray includes energy converters containing added atomic dopants in the crystalline lattice. Figures 1A and 1B show how a crystalline lattice of a crystalline material can be doped with elements having high atomic mass. Figure 1A provides a graphical representation of a crystalline material along a crystalline plane, with each dot representing one atom in the crystalline matrix. Figure 1B provides a graphical representation of the same crystalline material, but containing dopant elements having a high atomic mass (represented by the dots having an “X” through them) which are doped by substitution in the crystalline lattice. [00104] A second category of method is by coating energy converting particles on their surface with a coating that contains a high atomic mass material doped therein. Any of the noted coatings above can be used as the surface coating, with any desired high atomic mass material being added as a dopant. Figures 2A and 2B provide graphical representations of a low atomic mass energy converting particle (20) with a surface coating (22), such as a DLC coating, for example, without the dopant (22a) (Figure 2A) and with the dopant (22b) (Figure 2B). Depending on the coating used, various methods of adding the dopant to the coating can be used. In the case of a DLC coating, for example, the DLC coating is typically formed by vapor phase deposition. During that vapor phase deposition, the high atomic mass dopant can be introduced by co-depositing the dopant while forming the DLC coating. Preferably, the high atomic mass dopant is a metallic element having an atomic mass higher than 20, and is more preferably a transition element. [00105] In a third category, one can use composite particles that have a combination of the energy converters (30) mixed with particles made of a high enough atomic mass material (32). Figures 3A-3C provide graphical representations of this embodiment. Figure 3A shows particles of the energy converter having low atomic mass (i.e. difficult to detect using X-ray imaging) (30) and particles of a high atomic mass material (i.e. readily detectible by X-ray imaging) (32) that have been sized and mixed using a ball-mill to provide a dispersed mixture. A polymer binder or resin is then applied to the mixture to form an encapsulation (34) around particles of the energy converter (30) and high atomic mass material (32), as shown in Figure 3B. A coating (36), such as a DLC coating is then formed over this polymer binder (34) encapsulated mixture, resulting in composite particles as shown in Figure 3C. [00106] In a fourth category, one can simply use a mixture of particles of the energy converter having low atomic mass with particles of a high atomic mass material. Figure 4 provides a graphical representation of such a mixture, showing a plurality of energy converter 24 6240479.1 particles (40) having a coating (42) such as a DLC coating, combined with particles of a high atomic mass material (44) which is preferably also coated with the coating (42) such as a DLC coating. While the coatings (42) on the energy converter particles (40) and high atomic mass material particles (44) are depicted as the same, one can also use different coatings on the two types of particles if desired. [00107] In a fifth category, one can prepare an energy converter particle having a coating on the particle surface formed from a conventional imaging contrast agent. Figure 5a provides a graphical representation of such particles, showing a plurality of energy converter particles (50) each having a coating (58) formed from a contrast agent. Interestingly, in this embodiment, the contrast agent coating (58) can be configured to be dissolvable within the body of the subject. The thus dissolved contrast agent gets filtered from the patient’s blood stream and excreted from the patient’s body by the normal waste elimination processes. Figure 5B provides a graphical representation of one modification of these particles, in which the energy converter particles (50) are first covered with a high transmissibility coating (52), preferably of DLC or another biologically compatible and inert material, before forming the coating (58) of the contrast agent. In this embodiment, once the contrast agent has dissolved in the subject’s body, the remaining energy converter particle still has the biologically compatible/inert coating thus avoiding potential toxicity of the energy converter material itself. In these embodiments, a variety of conventional contrast agents can be used to form the coating on the energy converter particles, such as: [00108] Iodine based contrast agents: these are the most widely used contrast agents in CT imaging. Iodine-based contrast agents are conventionally administered intravenously to enhance the visibility of blood vessels and specific organs, such as the brain, liver, and kidneys. They help to improve the differentiation of blood vessels from surrounding tissues and can aid in the detection of various abnormalities, including tumors, vascular conditions, and other pathologies. In the present invention, it is only necessary to provide a very low level of this contrast agent on the surfaces of low atomic mass energy converting particles to enable their imaging. [00109] Barium Sulfate: Although primarily used in X-ray imaging, barium sulfate can also be used as a contrast agent in CT imaging for certain conditions involving the gastrointestinal tract. Conventionally, patients may ingest or be administered barium sulfate orally or rectally to help visualize the lining of the digestive tract and identify abnormalities, such as tumors, ulcers, and other gastrointestinal pathologies. In the present invention, it is only necessary to 25 6240479.1 provide a very low level of this contrast agent on the surfaces of low atomic mass energy converting particles to enable their imaging. [00110] Gadolinium based contrast agents: while these agents are more commonly used in magnetic resonance imaging (MRI), gadolinium-based contrast agents can also be used for certain X-ray procedures. They are particularly useful in enhancing the visibility of specific tissues, such as the brain, spine, and joints. In the present invention, it is only necessary to provide a very low level of this contrast agent on the surfaces of low atomic mass energy converting particles to enable their imaging. [00111] Hence, the contrast agent coatings on the energy converter particles can be very thin and still provide significant improvements in imaging, while enabling their dissolution and elimination from the body in a suitably short period of time. [00112] As an example of the third category above, particles were prepared having a structure according to Fig.3B, wherein the energy converting material (30) was a halophosphate material having structure (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺), the high atomic mass material (32) was a metal, namely copper, and the encapsulation (34) was prepared using an ethyl cellulose resin. The resulting composition was then measured for its UV emissions. [00113] As a further example of the third category, particles were prepared similarly wherein the energy converting material (30) was YTaO4, with and without the copper as the high atomic mass material (32). The same encapsulation resin of ethyl cellulose was used. Fig.6 provides a graphical representation of the improvements in emissions and thus imaging using these two materials, in the presence of the high atomic mass material. Fig.6 shows (i) the results for the halophosphate material in the absence of the high atomic mass copper (the bottom line of the graph) and the prepared particles having the high atomic mass copper (top line of the graph, data points marked as “X”), and (ii) the results for the YTaO4 material without copper is shown in the line having data points marked as “+”, while the YTaO4 material combined with copper is shown in the line having data points marked as “_*”. As shown, the presence of the high atomic mass copper material provided

in emissions, and thus in imaging, in the 60 kVp regime regardless of the identity of the energy converter. [00114] Accordingly, the present invention is exemplified, but not limited to, at least the following listing of embodiments: 26 6240479.1 _{Embodiment 1. A method for enhancing radioimaging of a coated energy} modulation agent, comprising: coating a dried energy modulation agent with a coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, wherein the coating comprises one or more contrast agents in an amount sufficient to enhance radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent. E_{mbodiment 2. The method of Embodiment 1, wherein the coating is a} diamond or diamond-like carbon (DLC) coating. E_{mbodiment 3. The method of Embodiment 1, wherein the coating is a member} selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co- glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)- poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. E_{mbodiment 4. The method of any one of Embodiments 1 to 3, wherein the one} or more contrast agents are incorporated into the coating as dopants during formation of the coating. E_{mbodiment 5. The method of any one of Embodiments 1 to 3, wherein the one} or more contrast agents are one or more submicron sized contrast agents. E_{mbodiment 6. The method of Embodiment 5, wherein the one or more} submicron sized contrast agents is selected from the group consisting of metal nanoparticles, lanthanide compound nanoparticles, metallic compound nanoparticles, polymeric nanoparticles, polymeric nanocapsules, and combinations thereof. E_{mbodiment 7. The method of one of Embodiment 5 or Embodiment 6,} wherein the one or more submicron sized contrast agents is gold-based nanoparticles, copper- based nanoparticles, tantalum-based nanoparticles, bismuth-based nanoparticles, iron-based nanoparticles, platinum-based nanoparticles, barium-based nanoparticles, lead-based nanoparticles, uranium-based nanoparticles, silver-based nanoparticles, and combinations, compounds, and alloys thereof. 27 6240479.1 _{Embodiment 8. The method of any one of Embodiments 5 to 7, wherein the one} or more submicron sized contrast agents is lanthanide compound nanoparticles. E_{mbodiment 9. The method of Embodiment 8, wherein the lanthanide} compound nanoparticles are nanoparticles of gadolinium compounds, dysprosium compounds, ytterbium compounds, europium compounds, terbium compounds, yttrium compounds, or combinations thereof. E_{mbodiment 10. The method of any one of Embodiments 1 to 9, wherein the} coating is applied to a thickness of 60 nm to 115 nm. E_{mbodiment 11. The method of Embodiment 10, wherein the coating is applied} to a target setpoint thickness of 70 nm. E_{mbodiment 12. The method of Embodiment 10, wherein the coating is applied} to a thickness of 60 nm to 90 nm. E_{mbodiment 13. The method of any one of Embodiments 1 to 12, further} comprising coating the dried energy modulation agent with an ethyl cellulose coating prior to the coating having high transmissibility. E_{mbodiment 14. The method of any one of Embodiments 1 to 13, wherein the} energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 15. The method of Embodiment 14, wherein the combination of} two or more energy modulation agents is an admixture of Zn2SiO4:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 16. The method of Embodiment 15, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 17. The method of Embodiment 16, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 18. The method of Embodiment 17, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 19. A coated energy modulation agent prepared by the method of} any one of Embodiments 1 to 18. E_{mbodiment 20. The coated energy modulation agent of Embodiment 19,} wherein the coated energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 21. The coated energy modulation agent of Embodiment 20,} wherein the two or more energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and 28 6240479.1 (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1 E_{mbodiment 22. The coated energy modulation agent of Embodiment 21,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 23. The coated energy modulation agent of Embodiment 22,} wherein the ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 24. The coated energy modulation agent of Embodiment 23,} wherein the ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 25. A method for enhancing radioimaging of a coated energy} modulation agent, comprising: coating a dried energy modulation agent with a first coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, and applying a second coating on the first coating, wherein the second coating comprises one or more contrast agents, wherein the second coating enhances radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent. E_{mbodiment 26. The method of Embodiment 25, wherein the one or more} contrast agents is one or more members selected from the group consisting of liposomal contrast agents, contrast agent containing nanoemulsions, contrast agent containing nanosuspensions, contrast agent containing nanocapsules, and combinations thereof. E_{mbodiment 27. The method of one of Embodiments 25 or 26, wherein the first} coating is a diamond or diamond-like carbon (DLC) coating. E_{mbodiment 28. The method of one of Embodiments 25 or 26, wherein the first} coating is a member selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. 29 6240479.1 _{Embodiment 29. The method of any one of Embodiments 25 to 28, wherein the} first coating is applied to a thickness of 60 nm to 115 nm. E_{mbodiment 30. The method of Embodiment 29, wherein the first coating is} applied to a target setpoint thickness of 70 nm. E_{mbodiment 31. The method of Embodiment 29, wherein the first coating is} applied to a thickness of 60 nm to 90 nm. E_{mbodiment 32. The method of any one of Embodiments 25 to 31, further} comprising coating the dried energy modulation agent with an ethyl cellulose coating prior to the first coating. E_{mbodiment 33. The method of any one of Embodiments 25 to 32, wherein the} energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 34. The method of Embodiment 33, wherein the combination of} two or more energy modulation agents is an admixture of Zn2SiO4:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 35. The method of Embodiment 34, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 36. The method of Embodiment 35, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 37. The method of Embodiment 36, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 38. A coated energy modulation agent prepared by the method of} any one of Embodiments 25 to 37. E_{mbodiment 39. The coated energy modulation agent of Embodiment 38,} wherein the coated energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 40. The coated energy modulation agent of Embodiment 39,} wherein the two or more energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1 E_{mbodiment 41. The coated energy modulation agent of Embodiment 40,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 42. The coated energy modulation agent of Embodiment 41,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 30 6240479.1 _{Embodiment 43. The coated energy modulation agent of Embodiment 42,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 44. A method for enhancing radioimaging of an energy} modulation agent, comprising: forming a coating on a surface of particles of the energy modulation agent, wherein the coating comprises one or more contrast agents. E_{mbodiment 45. The method of Embodiment 44, wherein the one or more} contrast agents are configured to be dissolvable and readily eliminated from a subject within a predetermined period of time after administration of the thus coated energy modulation agent. E_{mbodiment 46. The method of one of Embodiments 44 or 45, wherein the} energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 47. The method of Embodiment 46, wherein the combination of} two or more energy modulation agents is an admixture of Zn₂SiO₄:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 48. The method of Embodiment 47, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 49. The method of Embodiment 48, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 50. The method of Embodiment 49, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 51. A coated energy modulation agent prepared by the method of} any one of Embodiments 44 to 50. E_{mbodiment 52. The coated energy modulation agent of Embodiment 51,} wherein the coated energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 53. The coated energy modulation agent of Embodiment 52,} wherein the two or more energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 54. The coated energy modulation agent of Embodiment 53,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 31 6240479.1 _{Embodiment 55. The coated energy modulation agent of Embodiment 54,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 56. The coated energy modulation agent of Embodiment 55,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 57. A method for enhancing radioimaging of an energy modulation} agent, comprising: forming a crystalline energy modulation agent having incorporated therein an imageable amount of one or more high atomic mass dopants in a crystalline lattice of the crystalline energy modulation agent. E_{mbodiment 58. The method of Embodiment 57, wherein the crystalline energy} modulation agent has, on a surface thereof, a coating having high transmissibility at a wavelength of primary emission from the crystalline energy modulation agent. E_{mbodiment 59. The method of Embodiment 58, wherein the coating is a} diamond or diamond-like carbon (DLC) coating. E_{mbodiment 60. The method of Embodiment 58, wherein the coating is a} member selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. E_{mbodiment 61. The method of any one of Embodiments 57-60, wherein the} one or more high atomic mass dopants have an atomic mass higher than 20. E_{mbodiment 62. The method of any one of Embodiments 57-61, wherein the} one or more high atomic mass dopants comprise one or more transition elements. E_{mbodiment 63. The method of any one of Embodiments 57-62, wherein the} one or more high atomic mass dopants comprise one or more lanthanide elements. E_{mbodiment 64. The method of any one of Embodiments 57-63, wherein the} energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 65. The method of Embodiment 64, wherein the combination of} two or more energy modulation agents is an admixture of Zn2SiO4:Mn²⁺and 32 6240479.1 (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 66. The method of Embodiment 65, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 67. The method of Embodiment 66, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 68. The method of Embodiment 67, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 69. A coated energy modulation agent prepared by the method of} any one of Embodiments 57 to 68. E_{mbodiment 70. The coated energy modulation agent of Embodiment 69,} wherein the coated energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 71. The coated energy modulation agent of Embodiment 70,} wherein the two or more energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 72. The coated energy modulation agent of Embodiment 71,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 73. The coated energy modulation agent of Embodiment 72,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 74. The coated energy modulation agent of Embodiment 73,} wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 75. A method for enhancing radioimaging of an energy modulation} agent particle mixture, comprising: mixing a first plurality of particles comprising one or more energy modulation agents with a second plurality of particles comprising one or more high atomic mass materials to provide the energy modulation agent particle mixture having enhanced radioimageability. E_{mbodiment 76. The method of Embodiment 75, wherein the first plurality of} particles has, on a surface of the particles, a first biocompatible coating having high transmissibility at a wavelength of primary emission from the one or more energy modulation agents. 33 6240479.1 _{Embodiment 77. The method of one of Embodiment 75 or Embodiment 76,} wherein the second plurality of particles has, on a surface of the particles, a second biocompatible coating. E_{mbodiment 78. The method of Embodiment 77, wherein both the first plurality} of particles and the second plurality of particles have biocompatible coatings, wherein the first biocompatible coating on the first plurality of particles may be the same as or different from the second biocompatible coating on the second plurality of particles. E_{mbodiment 79. The method of any one of Embodiments 76-78, wherein the} first and/or second biocompatible coating is a diamond or diamond-like carbon (DLC) coating. E_{mbodiment 80. The method of any one of Embodiments 76-79, wherein the} first and/or second biocompatible coating is a member selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. E_{mbodiment 81. The method of any one of Embodiments 75-80, wherein the} one or more high atomic mass materials have an atomic mass higher than 20. E_{mbodiment 82. The method of any one of Embodiments 75-81, wherein the} one or more high atomic mass materials comprise one or more transition elements. E_{mbodiment 83. The method of any one of Embodiments 75-82, wherein the} one or more high atomic mass materials comprise one or more lanthanide elements. E_{mbodiment 84. The method of any one of Embodiments 75-83, wherein the} energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 85. The method of Embodiment 84, wherein the combination of} two or more energy modulation agents is an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 86. The method of Embodiment 85, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 34 6240479.1 _{Embodiment 87. The method of Embodiment 86, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 88. The method of Embodiment 87, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 89. An energy modulation agent particle mixture prepared by the} method of any one of Embodiments 75 to 88. E_{mbodiment 90. The energy modulation agent particle mixture of Embodiment} 89, wherein the coated energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 91. The energy modulation agent particle mixture of Embodiment} 90, wherein the two or more energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 92. The energy modulation agent particle mixture of Embodiment} 91, wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 93. The energy modulation agent particle mixture of Embodiment} 92, wherein the ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 94. The energy modulation agent particle mixture of Embodiment} 93, wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 95. A method for preparing an energy converting composite} particle having enhanced radioimaging characteristics, comprising: providing a dispersed particle mixture comprising a first plurality of particles of one or more energy modulation agents and a second plurality of particles of one or more high atomic mass materials; and mixing the dispersed particle mixture with a polymer binder to encapsulate one or more of the first plurality of particles and one or more of the second plurality of particles within the polymer binder, thus providing a plurality of energy converting composite particles each containing one or more energy modulation agents and one or more high atomic mass materials. E_{mbodiment 96. The method of Embodiment 95, further comprising applying to} a surface of the energy converting composite particles a coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation. 35 6240479.1 _{Embodiment 97. The method of Embodiment 96, wherein the coating is a} biocompatible coating. E_{mbodiment 98. The method of one of Embodiment 96 or Embodiment 97,} wherein the coating is a diamond or diamond-like carbon (DLC) coating. E_{mbodiment 99. The method of any one of Embodiments 96-98, wherein the} coating is a member selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. E_{mbodiment 100. The method of any one of Embodiments 95-99, wherein the} one or more high atomic mass materials have an atomic mass higher than 20. E_{mbodiment 101. The method of any one of Embodiments 95-100, wherein the} one or more high atomic mass materials comprise one or more transition elements. E_{mbodiment 102. The method of any one of Embodiments 95-101, wherein the} one or more high atomic mass materials comprise one or more lanthanide elements. E_{mbodiment 103. The method of any one of Embodiments 95-102, wherein the} energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 104. The method of Embodiment 103, wherein the combination of} two or more energy modulation agents is an admixture of Zn2SiO4:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 105. The method of Embodiment 104, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 106. The method of Embodiment 105, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 107. The method of Embodiment 106, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. E_{mbodiment 108. An energy modulation agent particle mixture prepared by the} method of any one of Embodiments 95 to 107. 36 6240479.1 _{Embodiment 109. The energy modulation agent particle mixture of Embodiment} 108, wherein the coated energy modulation agent is a combination of two or more energy modulation agents. E_{mbodiment 110. The energy modulation agent particle mixture of Embodiment} 109, wherein the two or more energy modulation agents are an admixture of Zn₂SiO₄:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. E_{mbodiment 111. The energy modulation agent particle mixture of Embodiment} 110, wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. E_{mbodiment 112. The energy modulation agent particle mixture of Embodiment} 111, wherein the ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. E_{mbodiment 113. The energy modulation agent particle mixture of Embodiment} 112, wherein the ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. [00115] Numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein. 37 6240479.1

Claims

CLAIMS: 1_{. A method for enhancing radioimaging of a coated energy modulation agent,} comprising: coating a dried energy modulation agent with a coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, wherein the coating comprises one or more contrast agents in an amount sufficient to enhance radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent. 2_{. The method of claim 1, wherein the coating is a diamond or diamond-like} carbon (DLC) coating. 3_{. The method of claim 1, wherein the coating is a member selected from the} group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. 4_{. The method of any one of claims 1 to 3, wherein the one or more contrast} agents are incorporated into the coating as dopants during formation of the coating. 5_{. The method of any one of claims 1 to 3, wherein the one or more contrast} agents are one or more submicron sized contrast agents. 6_{. The method of claim 5, wherein the one or more submicron sized contrast} agents is selected from the group consisting of metal nanoparticles, lanthanide compound nanoparticles, metallic compound nanoparticles, polymeric nanoparticles, polymeric nanocapsules, and combinations thereof. 7_{. The method of one of claim 5 or claim 6, wherein the one or more submicron} sized contrast agents is gold-based nanoparticles, copper-based nanoparticles, tantalum-based nanoparticles, bismuth-based nanoparticles, iron-based nanoparticles, platinum-based nanoparticles, barium-based nanoparticles, lead-based nanoparticles, uranium-based nanoparticles, silver-based nanoparticles, and combinations, compounds, and alloys thereof. 8_{. The method of any one of claims 5 to 7, wherein the one or more submicron} sized contrast agents is lanthanide compound nanoparticles. 38 6240479.1

_{9. The method of claim 8, wherein the lanthanide compound nanoparticles are} nanoparticles of gadolinium compounds, dysprosium compounds, ytterbium compounds, europium compounds, terbium compounds, yttrium compounds, or combinations thereof. 1_{0. The method of any one of claims 1 to 9, wherein the coating is applied to a} thickness of 60 nm to 115 nm. 1_{1. The method of claim 10, wherein the coating is applied to a target setpoint} thickness of 70 nm. 1_{2. The method of claim 10, wherein the coating is applied to a thickness of 60} nm to 90 nm. 1_{3. The method of any one of claims 1 to 12, further comprising coating the dried} energy modulation agent with an ethyl cellulose coating prior to the coating having high transmissibility. 1_{4. The method of any one of claims 1 to 13, wherein the energy modulation} agent is a combination of two or more energy modulation agents. 1_{5. The method of claim 14, wherein the combination of two or more energy} modulation agents is an admixture of Zn₂SiO₄:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 1_{6. The method of claim 15, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 1_{7. The method of claim 16, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 1_{8. The method of claim 17, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 1_{9. A coated energy modulation agent prepared by the method of any one of} claims 1 to 18. 2_{0. The coated energy modulation agent of claim 19, wherein the coated energy} modulation agent is a combination of two or more energy modulation agents. 2_{1. The coated energy modulation agent of claim 20, wherein the two or more} energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1 2_{2. The coated energy modulation agent of claim 21, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 2_{3. The coated energy modulation agent of claim 22, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 39 6240479.1

_{24. The coated energy modulation agent of claim 23, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 2_{5. A method for enhancing radioimaging of a coated energy modulation agent,} comprising: coating a dried energy modulation agent with a first coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation, and applying a second coating on the first coating, wherein the second coating comprises one or more contrast agents, wherein the second coating enhances radioimaging of the coated energy modulation agent, while permitting the wavelength of primary emission to be effectively emitted from the coated energy modulation agent. 2_{6. The method of claim 25, wherein the one or more contrast agents is one or} more members selected from the group consisting of liposomal contrast agents, contrast agent containing nanoemulsions, contrast agent containing nanosuspensions, contrast agent containing nanocapsules, and combinations thereof. 2_{7. The method of one of claims 25 or 26, wherein the first coating is a diamond} or diamond-like carbon (DLC) coating. 2_{8. The method of one of claims 25 or 26, wherein the first coating is a member} selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co- glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)- poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. 2_{9. The method of any one of claims 25 to 28, wherein the first coating is applied} to a thickness of 60 nm to 115 nm. 3_{0. The method of claim 29, wherein the first coating is applied to a target} setpoint thickness of 70 nm. 3_{1. The method of claim 29, wherein the first coating is applied to a thickness of} 60 nm to 90 nm. 40 6240479.1

_{32. The method of any one of claims 25 to 31, further comprising coating the} dried energy modulation agent with an ethyl cellulose coating prior to the first coating. 3_{3. The method of any one of claims 25 to 32, wherein the energy modulation} agent is a combination of two or more energy modulation agents. 3_{4. The method of claim 33, wherein the combination of two or more energy} modulation agents is an admixture of Zn₂SiO₄:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 3_{5. The method of claim 34, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 3_{6. The method of claim 35, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 3_{7. The method of claim 36, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 3_{8. A coated energy modulation agent prepared by the method of any one of} claims 25 to 37. 3_{9. The coated energy modulation agent of claim 38, wherein the coated energy} modulation agent is a combination of two or more energy modulation agents. 4_{0. The coated energy modulation agent of claim 39, wherein the two or more} energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1 4_{1. The coated energy modulation agent of claim 40, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 4_{2. The coated energy modulation agent of claim 41, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 4_{3. The coated energy modulation agent of claim 42, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is about 1:2. 4_{4. A method for enhancing radioimaging of an energy modulation agent,} comprising: forming a coating on a surface of particles of the energy modulation agent, wherein the coating comprises one or more contrast agents. 4_{5. The method of claim 44, wherein the one or more contrast agents are} configured to be dissolvable and readily eliminated from a subject within a predetermined period of time after administration of the thus coated energy modulation agent. 41 6240479.1

_{46. The method of one of claims 44 or 45, wherein the energy modulation agent is} a combination of two or more energy modulation agents. 4_{7. The method of claim 46, wherein the combination of two or more energy} modulation agents is an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 4_{8. The method of claim 47, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 4_{9. The method of claim 48, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 5_{0. The method of claim 49, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 5_{1. A coated energy modulation agent prepared by the method of any one of} claims 44 to 50. 5_{2. The coated energy modulation agent of claim 51, wherein the coated energy} modulation agent is a combination of two or more energy modulation agents. 5_{3. The coated energy modulation agent of claim 52, wherein the two or more} energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 5_{4. The coated energy modulation agent of claim 53, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 5_{5. The coated energy modulation agent of claim 54, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 5_{6. The coated energy modulation agent of claim 55, wherein the ratio of} Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is about 1:2. 5_{7. A method for enhancing radioimaging of an energy modulation agent,} comprising: forming a crystalline energy modulation agent having incorporated therein an imageable amount of one or more high atomic mass dopants in a crystalline lattice of the crystalline energy modulation agent. 5_{8. The method of claim 57, wherein the crystalline energy modulation agent has,} on a surface thereof, a coating having high transmissibility at a wavelength of primary emission from the crystalline energy modulation agent. 5_{9. The method of claim 58, wherein the coating is a diamond or diamond-like} carbon (DLC) coating. 42 6240479.1

_{60. The method of claim 58, wherein the coating is a member selected from the} group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. 6_{1. The method of any one of claims 57-60, wherein the one or more high atomic} mass dopants have an atomic mass higher than 20. 6_{2. The method of any one of claims 57-61, wherein the one or more high atomic} mass dopants comprise one or more transition elements. 6_{3. The method of any one of claims 57-62, wherein the one or more high atomic} mass dopants comprise one or more lanthanide elements. 6_{4. The method of any one of claims 57-63, wherein the energy modulation agent} is a combination of two or more energy modulation agents. 6_{5. The method of claim 64, wherein the combination of two or more energy} modulation agents is an admixture of Zn₂SiO₄:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 6_{6. The method of claim 65, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 6_{7. The method of claim 66, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 6_{8. The method of claim 67, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 6_{9. A coated energy modulation agent prepared by the method of any one of} claims 57 to 68. 7_{0. The coated energy modulation agent of claim 69, wherein the coated energy} modulation agent is a combination of two or more energy modulation agents. 7_{1. The coated energy modulation agent of claim 70, wherein the two or more} energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 7_{2. The coated energy modulation agent of claim 71, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 43 6240479.1

_{73. The coated energy modulation agent of claim 72, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 7_{4. The coated energy modulation agent of claim 73, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 7_{5. A method for enhancing radioimaging of an energy modulation agent particle} mixture, comprising: mixing a first plurality of particles comprising one or more energy modulation agents with a second plurality of particles comprising one or more high atomic mass materials to provide the energy modulation agent particle mixture having enhanced radioimageability. 7_{6. The method of claim 75, wherein the first plurality of particles has, on a} surface of the particles, a first biocompatible coating having high transmissibility at a wavelength of primary emission from the one or more energy modulation agents. 7_{7. The method of one of claim 75 or claim 76, wherein the second plurality of} particles has, on a surface of the particles, a second biocompatible coating. 7_{8. The method of claim 77, wherein both the first plurality of particles and the} second plurality of particles have biocompatible coatings, wherein the first biocompatible coating on the first plurality of particles may be the same as or different from the second biocompatible coating on the second plurality of particles. 7_{9. The method of any one of claims 76-78, wherein the first and/or second} biocompatible coating is a diamond or diamond-like carbon (DLC) coating. 8_{0. The method of any one of claims 76-79, wherein the first and/or second} biocompatible coating is a member selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)-poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. 8_{1. The method of any one of claims 75-80, wherein the one or more high atomic} mass materials have an atomic mass higher than 20. 8_{2. The method of any one of claims 75-81, wherein the one or more high atomic} mass materials comprise one or more transition elements. 44 6240479.1

_{83. The method of any one of claims 75-82, wherein the one or more high atomic} mass materials comprise one or more lanthanide elements. 8_{4. The method of any one of claims 75-83, wherein the energy modulation agent} is a combination of two or more energy modulation agents. 8_{5. The method of claim 84, wherein the combination of two or more energy} modulation agents is an admixture of Zn₂SiO₄:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 8_{6. The method of claim 85, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 8_{7. The method of claim 86, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 8_{8. The method of claim 87, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 8_{9. An energy modulation agent particle mixture prepared by the method of any} one of claims 75 to 88. 9_{0. The energy modulation agent particle mixture of claim 89, wherein the coated} energy modulation agent is a combination of two or more energy modulation agents. 9_{1. The energy modulation agent particle mixture of claim 90, wherein the two or} more energy modulation agents are an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 9_{2. The energy modulation agent particle mixture of claim 91, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 9_{3. The energy modulation agent particle mixture of claim 92, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 9_{4. The energy modulation agent particle mixture of claim 93, wherein the ratio of} Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 9_{5. A method for preparing an energy converting composite particle having} enhanced radioimaging characteristics, comprising: providing a dispersed particle mixture comprising a first plurality of particles of one or more energy modulation agents and a second plurality of particles of one or more high atomic mass materials; and mixing the dispersed particle mixture with a polymer binder to encapsulate one or more of the first plurality of particles and one or more of the second plurality of particles 45 6240479.1 within the polymer binder, thus providing a plurality of energy converting composite particles each containing one or more energy modulation agents and one or more high atomic mass materials. 9_{6. The method of claim 95, further comprising applying to a surface of the} energy converting composite particles a coating having high transmissibility at a wavelength of primary emission from the energy modulation agent upon excitation. 9_{7. The method of claim 96, wherein the coating is a biocompatible coating.} _{98. The method of one of claim 96 or claim 97, wherein the coating is a diamond} or diamond-like carbon (DLC) coating. 9_{9. The method of any one of claims 96-98, wherein the coating is a member} selected from the group consisting of silica, phosphate, silicon oxynitride, silk, cellulose, bacterial cells, agarose gel, polyethylene glycol (PEG) and derivatives thereof, alginate, poly(L-lactic acid) (PLLA), poly(lactic acid) (PLA), polycaprolactone (PCL), poly(lactic-co- glycolic acid) (PLGA), polydimethylsiloxane (PDMS), poly(octamethylene citrate)- poly(octamethylene maleate citrate) (POC-POMC), cyclic olefin copolymer (COC), polycarbonate (PC), conductive polyethylene (CPE), a biocompatible layer-by-layer assembly of bovine serum albumin (BSA) and tannic acid (TA), and methyltriethoxysilane/trimethoxymethylsilane. 1_{00. The method of any one of claims 95-99, wherein the one or more high atomic} mass materials have an atomic mass higher than 20. 1_{01. The method of any one of claims 95-100, wherein the one or more high atomic} mass materials comprise one or more transition elements. 1_{02. The method of any one of claims 95-101, wherein the one or more high atomic} mass materials comprise one or more lanthanide elements. 1_{03. The method of any one of claims 95-102, wherein the energy modulation} agent is a combination of two or more energy modulation agents. 1_{04. The method of claim 103, wherein the combination of two or more energy} modulation agents is an admixture of Zn2SiO4:Mn²⁺and (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 1_{05. The method of claim 104, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 1_{06. The method of claim 105, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 46 6240479.1

_{107. The method of claim 106, wherein the ratio of Zn2SiO4:Mn2+ :} (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) is about 1:2. 1_{08. An energy modulation agent particle mixture prepared by the method of any} one of claims 95 to 107. 1_{09. The energy modulation agent particle mixture of claim 108, wherein the} coated energy modulation agent is a combination of two or more energy modulation agents. 1_{10. The energy modulation agent particle mixture of claim 109, wherein the two} or more energy modulation agents are an admixture of Zn₂SiO₄:Mn²⁺and (3Ca₃(PO₄)₂Ca(F, Cl)2: Sb³⁺, Mn²⁺) at a ratio of Zn2SiO4:Mn²⁺ : (3Ca3(PO4)2Ca(F, Cl)2: Sb³⁺, Mn²⁺) of from 1:10 to 10:1. 1_{11. The energy modulation agent particle mixture of claim 110, wherein the ratio} of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:5 to 5:1. 1_{12. The energy modulation agent particle mixture of claim 111, wherein the ratio} of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is from 1:2 to 2:1. 1_{13. The energy modulation agent particle mixture of claim 112, wherein the ratio} of Zn₂SiO₄:Mn²⁺ : (3Ca₃(PO₄)₂Ca(F, Cl)₂: Sb³⁺, Mn²⁺) is about 1:2. 47 6240479.1