WO2025207781A1 - Antibody radioisotope constructs - Google Patents

Abstract

The present disclosure is directed to antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties. Also provided are methods of treating a disease or disorder in a patient in need thereof using the antibody radioisotope constructs, and methods of diagnosing a disease or disorder in a patient using the antibody radioisotopes disclosed herein.

Description

32591/70242 ANTIBODY RADIOISOTOPE CONSTRUCTS FIELD OF THE INVENTION [0001] The present disclosure in the field of biochemistry, immunology, and medicine relates to antibodies (“Abs”) and other proteins specific to the urokinase plasminogen activator receptor (uPAR), conjugated to imaging or therapeutic radionuclides (e.g., radioisotopes) for the diagnosis or treatment of disease. BACKGROUND [0002] Radiopharmaceuticals typically contain a radioisotope attached to a targeting moiety or carrier. The radioisotope is carried to the target by the carrier where the radioisotope then decays. This decay emits radiation which can be detected to visualize the target area via imaging or deliver localized radiation doses for therapy. In the field of oncology, radioisotopes commonly used for diagnostic medical imaging decay by gamma or positron emission and are imaged with Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET) imaging respectively. For treatment of cancer, commonly used therapeutic radioisotopes decay by beta-decay, alpha-decay, or other radioactive decay mechanisms that cause cell death in the targeted disease. [0003] Promising radiopharmaceutical targets should be expressed in the target (e.g. a cancer) but rarely or minimally in normal healthy tissue. A significant body of evidence from in vitro and in vivo studies has established that the urokinase plasminogen activator (uPA) system is central to the process of metastasis, making the uPA system a promising target for diagnostic and therapeutic cancer drug development (Mazar et al., Angiogenesis 1999; 3: 15-32). In addition to uPA, its cell surface receptor (uPAR) is a suitable target for the design and development of cancer therapeutic and diagnostic agents (Mazar, AntiCancer Drugs 2001; 12: 397- 400) because uPAR is selectively expressed on metastatic tumor cells and angiogenic endothelial cells but rarely, if at all, on other cells. [0004] The urokinase plasminogen activator receptor (uPAR) has been demonstrated to be selectively upregulated in tumor cells, as well as tumor-associated endothelial, stromal, and inflammatory cells, in a variety of advanced solid tumor types (Mazar, Clin Cancer Res.2008; 14: 5649-55). In cancers such as breast, colon, pancreatic, stomach, brain, and ovary, uPAR has been observed both on the tumor and surrounding stroma with expression frequently highest at the invasive front of both primary and secondary lesions. [0005] uPAR overexpression is associated with poor prognosis in various cancer types and disease aggressiveness (Mazar, Anti-Cancer Drugs 2001; 12(5): 387-400, Mazar Clin Cancer Res.2008; 14: 5649-55). Elevated uPAR expression is often correlated with metastatic and aggressive disease (de Bock et al., Med Res Rev.2004; 24(1): 13-39, Mazar et al., Curr Pharm Des.2011; 17: 1970-8). Further, uPAR is rarely expressed in most adult quiescent tissue; when present, it is usually restricted to tissue resident aberrantly activated macrophages and monocytes, as well as remodeling epithelia, which is typically indicative of inflammation or wound healing. Therefore, targeting uPAR may provide a tumor-selective approach for the treatment of cancer 32591/70242 and a promising targeting agent for radiopharmaceuticals. [0006] Monoclonal antibodies (mAbs) that bind to uPA-uPAR complexes and that inhibit their interaction with downstream targets (such as integrins) have been developed previously. See: U.S. Pat.8,101,726 and 8,105,602 which are incorporated by reference in their entirety. [0007] Antibodies have a longer half-life in circulation compared to smaller molecules such as peptides which can be rapidly cleared via the kidneys and often accumulate in the target over a period of days, so a longer half- life radioisotope is preferable for conjugation. For diagnostic imaging, one such radioisotope is zirconium-89 with a valence of +4. ⁸⁹Zr emits a gamma ray (909 keV) and also a positron at about 397 keV, both emissions being useful in diagnostics with PET imaging the preferred imaging modality. The half-life of ⁸⁹Zr is 3.3 days, which is similar to the circulation half-lives of many monoclonal antibodies used in medicine. ⁸⁹Zr isotopes have been used in radiolabeling and evaluation of mAbs in positron emission tomography (Immuno-PET). (Saleem et al., Sci World J.2014; 269605: 9 pages.) The final decay product of ⁸⁹Zr is yttrium-89, a stable non-radioactive isotope. [0008] To attach ⁸⁹Zr to antibodies, desferrioxamine B (DFO) has been and continues to be the most commonly used chelator in human clinical studies (Joon et al, Int J Mol Sci.2020 Jun; 21(12): 4309). DFO is typically conjugated to the antibody via lysine-reactive bifunctional linkers including benzyl isothiocyanate-DFO (p-SCN-Bz-DFO) (Perk et al., Eur J Nucl Med Mol Imaging.2010; 37: 250–259) or tetrafluorophenyl-N-succinyl- DFO (Verel et al, J Nucl Med.2003; 44: 1271–1281). [0009] However, in vivo PET imaging studies of antibodies conjugated with ⁸⁹Zr-DFO have demonstrated problems with chelator stability resulting in the loss of the radioisotope from the DFO chelator and the accumulation of ⁸⁹Zr in the bone (Fischer at al., Molecules 2013; 18(6): 6469-6490). The in vivo behavior of ⁸⁹Zr (injected as ⁸⁹Zr-chloride) has been previously reported and exhibits a relatively slow clearance from the body with strong uptake in the bone and joints. Abou et al., Nucl Med Biol.2011; 38(5): 675–681, reported in a preclinical study injecting ⁸⁹Zr-chloride into mice that just 20% of the injected dose was cleared after 6 days, and the mice showed high and rapid bone uptake of 15% injected dose/gram at 8 hours post-injection (e.g., imaging a mouse treated with ⁸⁹Zr-chloride revealed that the whole mouse backbone is visible, for example) with only minor loss after 6 days. [0010] Recent research has focused on reducing DFO’s loss of ⁸⁹Zr to the bone using different chelators (Bhatt et al., Molecules, 2018; 23: 638). DFO’s lack of stability is a consequence of the hexadentate binding complex that is not ideally matched to ⁸⁹Zr, which prefers octadentate binding to all of ⁸⁹Zr’s available coordination sites. A new octadentate chelator, DFO*, was developed and evaluated in animals showing improved retention of the ⁸⁹Zr isotope with significantly reduced bone accumulation in studies by Berg et al., J Nucl Med.2020; 61: 453–460 and Chomet et al., Eur J Nucl Med Mol Imaging.2021; 48: 694–707. [0011] Despite the intense research focus on new chelators to reduce the loss of ⁸⁹Zr described by Bhatt et al., Molecules, 2018; 23: 638 the instability of the chelation of ⁸⁹Zr to antibodies using DFO can also be caused 32591/70242 by the cleavage of ⁸⁹Zr-DFO from the antibody (i.e. the loss of the chelator-radioisotope structure). However, the mechanisms behind this loss of DFO from the antibody and the means to address it are not well understood. [0012] Once cleaved from the antibody, Abou et al., Nucl Med Biol.2011; 38(5): 675–681 also showed the biodistribution of free ⁸⁹Zr-DFO is rapidly cleared via the kidney and excreted in the urine. Holland et al., J Nucl Med.2010; 51: 1293–1300 also reported similar findings of an injection of ⁸⁹Zr-DFO into mice with PET images acquired at 1 min and 4 min post injection that show immediate kidney and bladder clearance with no significant uptake in bone or any other organ. [0013] A need therefore exists for antibody radioisotope constructs having improved properties, such as increased in vivo stability. SUMMARY [0014] Provided herein are methods of imaging a tissue in a patient, comprising administering to the patient an effective amount of an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; and (ii) performing an imaging procedure to detect the antibody radioisotope construct in the tissue. In some embodiments, the radioisotope comprises ⁸⁹Zr, the chelating linker comprises DFO*-Sq, and/or the antibody moiety comprises MNPR-101. In some embodiments, the tissue is soft tissue. In some embodiments, the tissue is inflamed tissue, cancer tissue, or healthy tissue. In some embodiments, the tissue is cancer tissue. In some embodiments, the tissue comprises a tumor associated with one or more of lung cancer, ovarian cancer, prostate cancer, brain cancer, bladder cancer, head and neck cancer, pancreatic cancer, breast cancer, gastric, and colorectal cancer. In some embodiments, the tissue is pancreatic, colorectal, gastric, ovarian, breast, bladder, lung, bone marrow, or lymph node tissue. In some embodiments, the tissue is bone marrow. In some embodiments, the imaging procedure comprises Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). [0015] Also disclosed are methods of diagnosing a disease or disorder in a patient, comprising the steps of: (i) administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; (ii) measuring the level of radiation in a first tissue and a second tissue, measured in the patient 10 minutes to 30 days after said administering, said measuring comprising Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET); and (iii) diagnosing the disease or disorder if the ratio of radiation measured in the first tissue compared to the second tissue is greater than 1.5:1. Also disclosed are methods of assessing effectiveness of uPAR-targeted therapy against a disease or disorder in a patient, comprising the steps of: (i) administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; (ii) measuring the level of radiation in a first tissue and a second tissue, measured in the 32591/70242 patient 10 minutes to 30 days after said administering, said measuring comprising Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET); and (iii) treating the disease or disorder with uPAR targeted therapy if the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater. In some embodiments, the radioisotope comprises ⁸⁹Zr, the chelating linker comprises DFO*-Sq, and/or the antibody moiety comprises MNPR-101. In some embodiments, the disease or disorder is cancer. In some embodiments, the first tissue is tumor tissue and/or the second tissue is liver tissue. [0016] Further disclosed are antibody radioisotope constructs comprising: one or more radioisotopes (e.g., radioactive metal ions); one or more chelating linkers; and an antibody moiety selected from MNPR-101, MNPR- 102, and fragments thereof, wherein the one or more chelating linkers are attached to the antibody moiety through one or more linking moieties. In some embodiments, the radioisotope comprises ⁸⁹Zr, the chelating linker comprises DFO*-Sq, and/or the antibody moiety comprises MNPR-101. In some embodiments, the antibody moiety comprises MNPR-101-DFO*-Sq-⁸⁹Zr. In some embodiments, the antibody radioisotope constructs have a conjugate-to-antibody ratio (CAR), defined as the ratio of conjugates to antibodies in the sample of interest, greater than 1, such as between about 1 and about 5, between about 1 and about 2, or about 1.5. In yet other embodiments, the antibody radioisotope constructs have a conjugate-to-antibody ratio (CAR) of less than 1, such as between about 0.01 and about 1, or about 0.2. Also disclosed are drug products comprising an antibody radioisotope construct disclosed herein, one or more antibodies, and a pharmaceutically acceptable excipient. In various embodiments, the drug products further comprise one or more radioprotectants, a pharmaceutically acceptable carrier, or a combination thereof. [0017] Further disclosed are methods of treating a disease or disorder, e.g., cancer, in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of an antibody radioisotope construct or drug product disclosed herein. Also disclosed are methods of treating a disease or disorder, e.g., cancer, in a patient in need thereof, comprising: (i) diagnosing the disease or disorder by administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; (ii) measuring the amount of circulating antibody after administration; (iii) based on the amount of circulating antibody measured after administration, determining if the administered mass dose led to acceptable biodistribution for uPAR-targeted therapy or if it needs to be adjusted, and (iv) adjusting the amount of antibody radioisotope construct administered to the patient to achieve a desired clinical effect. Also disclosed are methods of treating cancer in a patient in need thereof, comprising: (i) diagnosing cancer in a patient by administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; (ii) diagnosing the patient with cancer if the ratio of radiation measured in a first tissue compared to a second tissue is 1.5:1 or greater, and (iii) administering to the patient a therapeutically-effective amount of a cancer therapeutic. BRIEF DESCRIPTION OF THE DRAWINGS 32591/70242 [0018] FIG.1 shows the structure of DFO-NCS. [0019] FIG.2 shows the structure of DFO*-Sq. [0020] FIG.3 shows a schematic representation of DFO*-Sq coupling to mAb and complexation with a metal (M) with valence (+X). [0021] FIG.4 shows ELISA results demonstrating relative potency of MNPR-101-DFO*-Sq compared to naked antibody (MNPR-101). [0022] FIG.5 shows the whole-body retention of MNPR-101-DFO-NCS-⁸⁹Zr vs MNPR-101-DFO*-Sq-⁸⁹Zr in a mouse model. [0023] FIG.6 shows the circulation of MNPR-101-DFO-NCS-⁸⁹Zr vs MNPR-101-DFO*-Sq-⁸⁹Zr in a mouse model. [0024] FIG.7 shows PET imaging showing loss of MNPR-101-DFO-NCS-⁸⁹Zr versus MNPR-101-DFO*-Sq- ⁸⁹Zr drug through bladder at early time point in a mouse model. [0025] FIG.8 shows PET imaging of MIA-PaCa2 (pancreatic cell line)-bearing murine tumor models after administration of MNPR-101-DFO-NCS-⁸⁹Zr (top panel) and MNPR-101-DFO*-Sq-⁸⁹Zr (bottom panel). [0026] FIG.9 shows PET imaging of MNPR-101-DFO*-Sq-⁸⁹Zr in two human patients with a rare adenocarcinoma, one with mass dose of 4.5mg mAb (left panel) vs. one with mass dose of 20mg mAb (right panel). [0027] FIG.10 shows PET imaging of MNPR-101-DFO*-Sq-⁸⁹Zr in a metastatic ovarian cancer patient, with an absence of rapid bladder clearance at 2h and strong and durable uptake at 7 days post injection. DETAILED DESCRIPTION [0028] The present disclosure is directed to radiopharmaceuticals (e.g., antibody radioisotope constructs) comprising a chelating linker (e.g., a bifunctional chelator) that binds to a radioisotope and links the radioisotope to an antibody moiety (e.g., a mAb) specific for human urokinase plasminogen activator receptor (uPAR). Also provided are radiopharmaceuticals (e.g., antibody radioisotope constructs) comprising a mAb specific for human uPAR to which is chelated to a radioisotope. In some embodiments, the antibody moiety (e.g., mAb) is MNPR- 101 (including Abs, antigen binding fragments such as single chain Abs (such as scFv)), non-Ab polypeptides and peptides, aptamers, etc., as well as small organic molecules, that have the property of binding to uPAR without inhibiting the binding of uPA as described in US 2023-0338590 A1, incorporated herein by reference in its entirety. The bifunctional chelator may be a 3 or 4 hydroxamate containing chelator; this includes, but is not limited to, deferoxamine-squaramide (DFO-squaramide or DFO-Sq), DFO*-squaramide (DFO*-Sq), or DFO*- activated ester (including but not limited to carbodiimide, NHS ester, fluorophenyl ester). Non-limiting examples of radioisotopes include but are not limited to ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ²¹³Bi, ²¹²Pb, ⁶⁷Cu,⁴⁴Sc, ⁶⁷Ga, ⁹⁰Y, ^99mTc, ^natEu, ^natGd, ¹⁷⁷Lu, ¹⁶¹Tb, ¹⁸⁶Re, and ¹⁸⁸Re. 32591/70242 Potential stability issue with p-SCN-Bn-DFO (DFO-NCS) [0029] p-SCN-Bn-DFO (shown in FIG.1) is a bifunctional chelator that attaches zirconium89 to antibody.^ p- SCN-Bn-DFO is attached to antibodies through the phenyl isocyanate that typically forms a robust, stable covalent bond with the amines of antibodies.^ ^Deferoxamine (DFO), also known as deferoxamine B or desferrioxamine, is a hexadentate ligand with three hydroxamate groups that provide six oxygen that coordinates to metals.^ Bellotti et al., Molecules 2021; 26 (11): 3255 had reviewed over 20 different metal complexes formed by DFO. [0030] The phenyl isothiocyanate of p-SCN-Bn-DFO moiety conjugates to the antibody or antibody fragment via a thiourea bond. Ideally, this thiourea bond forms a stable bond with the amine side chain of a lysine residue on the antibody. However, isothiocyanate can also conjugate to antibodies via the cysteine residue on the antibody, forming a less stable dithiocarbonate (Petri et al. RSC Adv., 2020; 10: 14928-14936) that may be susceptible to cleavage in vivo. Thiourea bonds are also susceptible to damage and cleavage due to radiation or radiolysis, which can affect the stability of the drug, resulting in a shorter shelf life and poor performance as a diagnostic agent in vivo. Cleavage of the thiourea bond causes the chelator-radioisotope moiety to separate from the antibody or targeting agent. This separated chelator-radioisotope is then untargeted when administered as an injection and is often quickly eliminated in the urine. [0031] The selectivity of the conjugation to the preferred lysine is predominately determined by the pH of the reaction solution with higher pH (pH 9.0-11) being desirable while cysteine binding increases at pH 6-8 (Petri et al. RSC Adv., 2020; 10: 14928-14936). However, even at higher pH, some binding to the cysteine still occurs and variations in the pH during manufacture can lead to unacceptably high levels of weaker cysteine binding. This is undesirable because it has been found with various isothiocyanate derivatives that the cysteine adducts can break apart and bind elsewhere (Karlsson et al. Sci Rep.2016; 6: 21203), which can cause separation and loss of the conjugated DFO (and its chelated ⁸⁹Zr) from the antibody. [0032] This breaking apart and binding elsewhere of isothiocyanate conjugated to cysteine may not be detected in in vitro stability assay of conjugated antibody because reattachment can occur to lysines or other amines on the same antibody. However, with respect to in vivo study, the rearrangement of isothiocyanate conjugated to cysteine has far more competing options to reform elsewhere. This will result in rapid breakdown and clearance. This was observed with DFO-NCS conjugated to the uPAR-targeted antibody, MNPR-101. [0033] The use of the bifunctional chelator p-SCN-Bz-DFO to form MNPR-101-DFO-NCS-⁸⁹Zr was previously disclosed and described by Mazar et al in U.S. Patent Application No.18/010,510 filed on June 15, 2021 incorporated herein by reference in its entirety. [0034] However, as discussed in the Background section above, radionuclide-DFO-antibodies are susceptible to loss of the radionuclide, especially to the bone. This may be driven by loss of the radionuclide itself, or cleavage of the radionuclide-DFO from the antibody (i.e. the loss of the chelator-radioisotope structure). The mechanisms behind this loss of DFO from the antibody, and the means to address it are not well understood, 32591/70242 and mitigating this loss, in particular when seen primarily in vivo, is the subject of the disclosure. Antibody Radioisotope Constructs [0035] The antibody radioisotope constructs disclosed herein are used to deliver radiation to a target tissue using a radioisotope (used interchangeably herein with the terms “radionuclide”). These antibody radioisotope constructs comprise three components: one or more radioisotopes, one or more chelating linkers, and one or more antibody moieties specific for human urokinase plasminogen activator receptor (uPAR). The antibody radioisotope constructs of the disclosure further have various structural features as discussed herein. [0036] In some cases, provided herein are antibody radioisotope constructs comprising: one or more radioisotopes; one or more chelating linkers; and an antibody moiety selected from MNPR-101, MNPR-102, and fragments thereof, wherein the one or more chelating linkers are attached to the antibody moiety through one or more linking moieties. Radioisotopes (Radionuclides) [0037] The antibody radioisotope constructs of the disclosure comprise one or more radioisotopes. The term “radioisotopes” as used herein refers to elemental isotopes that have excess numbers of either neutrons or protons, giving them excess nuclear energy, and making them unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferred to one of its electrons to release it as a conversion electron; or used to create and emit a new particle (alpha particle or beta particle) from the nucleus. During those processes, the radioisotope is said to undergo radioactive decay. This decay emits radiation which can be detected to visualize a target area via imaging or to deliver localized radiation doses for therapeutic applications. [0038] Nonlimiting examples of various radioisotopes useful herein include, but are not limited to, ⁴⁷Sc, ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ⁹⁰Y, ¹⁰⁹Pd, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁹⁹Au, ²¹¹At, ²¹²Pb, ²¹³Bi, ²²³Ra, ²²⁷Th, ¹⁶¹Tb, ¹⁷⁷Lu, or ²²⁵Ac. In some cases, the radioisotope is ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ²¹²Pb, ¹⁶¹Tb, ¹⁷⁷Lu, or ²¹³Bi. In some cases, the radioisotope is ⁸⁹Zr. [0039] In some embodiments, the radioisotope is ⁸⁹Zr. A further useful isotope in the present disclosure is indium-111, which also binds to DFO*, and is widely used for single photon emission computed tomography (SPECT) imaging. Indium has a valence of +3, and In-111 has a half-life of about 2.8 days. Indium-111 decay provides gamma rays of 0.171 MeV and 0.245 MeV, that can be used in diagnostic scans such as single photon emission computed tomography (SPECT) imaging. In-111 decays to cadmium-111, which is nonradioactive and stable. Other useful radioisotopes include but are not limited to ⁶⁸Ga, ⁶⁴Cu, and ⁶⁷Cu. [0040] The radioisotopes of the antibody radioisotope constructs of the disclosure are associated with the rest of the construct indirectly as part of a chelate, through the chelating linkers discussed herein. Chelating Linkers [0041] The antibody radioisotope constructs of the disclosure comprise one or more chelating linkers. The 32591/70242 term “chelating linker” used herein refers to a linker that is covalently attached to the antibody moiety of the antibody radioisotope constructs of the disclosure and which chelates the radioisotope, thus linking it to the antibody moiety. Suitable linkers are known in the art, and non-limiting examples of chelating linkers contemplated by the disclosure include diethylenetriamine pentaacetate (DTPA), deferoxamine (DFO), DFO*, tetraacetic acid (DOTA), and Macropa (e.g., Macropa-NCS). [0042] In various embodiments of the antibody radioisotope constructs of the disclosure, the chelating linker comprises one or more linking moieties that serves as a direct covalent connection between the linker and the antibody. Non-limiting examples of linking moieties contemplated herein include squaramide (i.e., 3,4- diaminocyclobut-3-ene-1,2-dione) moieties, triazole moieties (e.g., triazole moieties formed through a “click” reaction), one or more esters, and combinations thereof. In some embodiments, the linking moiety comprises a squaramide moiety. Thus, in embodiments, the chelating linker is attached to the antibody through the linking moiety (e.g., through a squaramide moiety). [0043] In some embodiments, the chelating linker comprises squaramide-modified diethylenetriamine pentaacetate (DTPA-Sq), squaramide-modified deferoxamine (DFO-Sq), squaramide-modified DFO* (DFO*-Sq), squaramide-modified dodecane tetraacetic acid (DOTA-Sq), or squaramide-modified Macropa (Macropa-Sq). In some embodiments, the chelating linker comprises one squaramide moiety. In some embodiments, the chelating linker comprises more than one squaramide moiety. In some embodiments, the chelating linker comprises one or more DFO*-Sq. In some embodiments, the chelating linker comprises one DFO*-Sq. [0044] In some embodiments, an average of one chelating linker (or chelating linker-radioisotope chelate) is associated with the antibody moiety, i.e., the antibody radioisotope construct has a conjugate-to-antibody ratio (“CAR”) of 1. In some embodiments, an average of more than one chelating linker (or chelating linker- radioisotope chelate) is associated with the antibody moiety, i.e., the antibody radioisotope construct has a conjugate-to-antibody ratio (CAR) of greater than 1. In some embodiments, the conjugate-to-antibody ratio (CAR) is between 1 and 5. In some embodiments, the conjugate-to-antibody ratio (CAR) is between 1 and 2. In some embodiments, the conjugate-to-antibody ratio (CAR) is about 1, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2. In some embodiments, the conjugate-to- antibody ratio (CAR) is about 1.5. In some embodiments, the conjugate-to-antibody ratio (CAR) is less than 1. In some embodiments, the conjugate-to-antibody ratio (CAR) is between 0.01 and 1. In some embodiments, the conjugate-to-antibody ratio (CAR) is between 0.1 and 1. In some embodiments, the conjugate-to-antibody ratio is about 1, about 0.8, about 0.6, about 0.5, about 0.4, about 0.3, about 0.2, or about 0.1. Antibody Moieties [0045] The antibody radioisotope constructs of the disclosure comprise an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR). The term “antibody moiety” used herein refers to an antibody, an antibody fragment, or a non-antibody uPAR-targeting protein. These antibody moieties are capable of selective targeting and binding to a human urokinase plasminogen activator receptor (uPAR). 32591/70242 [0046] uPAR is an ideal target for antibodies because it is expressed on the cell surface. Expression of uPAR at the tumor-vasculature interface (on invasive tumor cells, angiogenic endothelial cells, or tumor-associated macrophages), suggests that antibodies targeting this protein would not suffer the same barriers to diffusion that have led to the failure of other mAbs to enter tumors or tissues and serve as diagnostic agents or exert therapeutic effects. Importantly, uPAR is not normally expressed on quiescent tissues, which should minimize the potential for toxicity when employing a therapeutic Ab and minimize non-specific signals (or false positives) when employing a diagnostic Ab. [0047] Non-limiting examples of uPAR-targeting antibody moieties contemplated for use as the antibody moieties of the antibody radioisotope constructs of the disclosure include MNPR-101 or MNPR-102. In some embodiments, the antibody moiety is MNPR-101. [0048] While these mAbs showed utility as “naked” antibodies, the present disclosure focuses on their ability to target diagnostic and therapeutic agents, preferably diagnostic and therapeutic radionuclides (radioconjugates), to cancers expressing the urokinase plasminogen activator receptor. [0049] A murine and a humanized mAb, MNPR-101, that directly binds to uPAR with high affinity and specificity has been developed (see, for example, Mazar AP et al., Curr Pharm Des.2011;17: 1970-8; Marudamuthu AS et al., J Biol Chem.2015; 290:9428-41; and U.S. Pat.8,101,726). [0050] According to the present disclosure, MNPR-101 (or another uPAR specific mAb such as MNPR-102) serves as a scaffold to design uPAR-specific antibody radioisotope constructs, only to the alternatively activated myeloid immune cells expressing uPAR while sparing normal cells and tissue that do not express uPAR or express very low levels. [0051] MNPR-101 (previously known as huATN-658) is a humanized (96% human sequence) mAb developed against human uPAR. MNPR-101 targets a previously unidentified epitope in uPAR, which has been demonstrated to mimic the CD11b binding site on uPAR (Xu X et al., PLoS One.2014, 9: e85349). CD11b expression is a marker of myeloid immune cell activation (Pinsky MR, Contrib Nephrol.2001, 132:354-66), i.e., that of macrophages and neutrophils and is involved in myeloid cell adhesion and infiltration when it interacts with uPAR on these cells (Gu JM et al., J Cell Physiol.2005, 204:73-82). Variable (V) Region Amino Acid Sequences of two Preferred mAbs mAb MNPR 101 (formerly ATN-658): Variable region sequences [0052] The consensus amino acid sequence (single-letter code) of the light chain variable region (V_L) and heavy chain variable region (V_H) polypeptides of MNPR101 are shown below. The complementarity-determining regions (CDRs) for each variable region are highlighted (italic, bold, underscored) [0053] MNPR-101 V_L Protein (SEQ ID NO:1): 1 DIXLTQSPLT LSVTIGQPAS ISCKSSQSLL DSDGKTYLNW LLQRPGQSPK 51 RLIYLVSKLD SGVPDRFTGS GSGTDFTLKI SRVEAEDLGV YYCWQGTHFP 32591/70242 101 LTFGAGTKLE LKL [0054] MNPR-101 V_H Protein (SEQ ID NO:2) 1 VQLQESGPEL VKTGASVKIS CKASGYSFTS YYMHWVKQSH GKSLEWIGEI 51 NPYNGGASYN QKIKGRATFT VDTSSRTAYM QFNSLTSEDS AVYYCARSIY 101 GHSVLDYWGQ GTTVTVS TABLE 1: CDRs of MNPR-101 L and H Chains *CDR-L1: first CDR of L chain; CDR-H2: 2^nd CDR of H chain, etc. mAb MNPR-102: Variable region sequences [0055] Amino acid sequence (single-letter code) of the light chain (VL) and heavy chain (VH) variable regions of monoclonal antibody MNPR-102. The complementarity-determining regions (CDRs) for each variable region are highlighted (italic, bold, underscored). [0056] MNPR-102 VL Protein Sequence (SEQ ID NO:9) 1 DIVLTQSPDI TAASLGQKVT ITCSASSSVS YMHWYQQKSG TSPKPWIFEI 51 SKLASGVPAR FSGSGSGTSY SLTISSMEAE DAAIYYCQQW NYPFTFGGGT 101 KLEIKR [0057] MNPR-102 V_H Protein Sequence (SEQ ID NO:10) 1 VKLQQSGPEV VKPGASVKIS CKASGYSFTN FYIHWVKQRP GQGLEWIGWI 51 FHGSDNTEYN EKFKDKATLT ADTSSSTAYM QLSSLTSEDS AVYFCARWGP 101 HWYFDVWGQG TTVTVSS TABLE 2. CDRs of MNPR-102 32591/70242 *CDR-L1: first CDR of L chain; CDR-H2: 2^nd CDR of H chain, etc. [0058] According to the present disclosure, an Ab or mAb, has “essentially the same antigen-binding characteristics” as a reference mAb if it demonstrates a similar specificity profile (e.g., by rank order comparison), and has affinity for the relevant antigen (e.g., uPA-uPAR complex) within 1.5 orders of magnitude, more preferably within one order of magnitude, of the reference Ab. [0059] The antibodies and conjugates can be evaluated for direct anti-angiogenic activity in an in vivo Matrigel plug model. Radioiodinated antibodies and conjugates are used to test Ab internalization using, for example, MDA MB 231 cells which express both receptor and ligand. Antibody internalization is also measured in the presence of PAI-1:uPA complexes. TABLE 3. uPAR epitope sequences ¹The amino acid numbering reflects the processed form of uPAR Chimeric/Humanized Antibodies [0060] The chimeric antibodies of the disclosure comprise individual chimeric H and L Ig chains. The chimeric H chain comprises an antigen binding region derived from the H chain of a non-human Ab specific for e.g., uPA/uPAR or uPAR-integrin complex, for example, MNPR-101 or mAb MNPR-102, which is linked to at least a portion of a human C_H region. A chimeric L chain comprises an antigen binding region derived from the L chain of a non-human Ab specific for the target antigen, linked to at least a portion of a human C_L region. As used herein, the term “antigen binding region” refers to that portion of an Ab molecule which contains the amino acid residues that interact with an antigen and confer on the Ab its specificity and affinity for the antigen. The Ab region includes the “framework” amino acid residues necessary to maintain the proper conformation of the antigen-binding (or “contact”) residues. [0061] As used herein, the term “chimeric antibody” includes monovalent, divalent or polyvalent Igs. A monovalent chimeric Ab is an HL dimer formed by a chimeric H chain associated through disulfide bridges with a chimeric L chain. A divalent chimeric Ab is tetramer H2L2 formed by two HL dimers associated through at least 32591/70242 one disulfide bridge. A polyvalent chimeric Ab can also be produced, for example, by employing a C_H region that aggregates (e.g., from an IgM H chain, termed the µ chain). [0062] The disclosure also provides for “derivatives” of the mouse mAbs or the chimeric Abs, which term includes those proteins encoded by truncated or modified genes to yield molecular species functionally resembling the Ig fragments. [0063] Antibodies, fragments or derivatives having chimeric H chains and L chains of the same or different V region binding specificity, can be prepared by appropriate association of the individual polypeptide chains, as taught, for example by Sears et al., Proc. Natl. Acad. Sci. USA 72:353-357 (1975). With this approach, hosts expressing chimeric H chains (or their derivatives) are separately cultured from hosts expressing chimeric L chains (or their derivatives), and the Ig chains are separately recovered and then associated. Alternatively, the hosts can be co-cultured and the chains allowed to associate spontaneously in the culture medium, followed by recovery of the assembled Ig, fragment or derivative. [0064] The antigen binding region of the chimeric Ab (or a human mAb) of the present disclosure is derived preferably from a non-human Ab specific for e.g., uPA/uPAR or uPAR-integrin complex. Preferred sources for the DNA encoding such a non-human Ab include cell lines which produce Ab, preferably hybridomas. Preferred hybridomas are the MNPR-101 hybridoma cell line (ATCC Accession No. PTA-8191and MNPR-102 (ATCC Accession No. PTA 8192) whose V regions have the sequences shown above. [0065] Thus, a preferred chimeric Ab (or human Ab) has a VL sequence SEQ ID NO:1 and a VH sequence SEQ ID NO:2 which are the amino acid sequences of mAb MNPR-101. The residues of these V regions that are not in the CDR regions may be varied, preferably as conservative substitutions, as long as the V region results in an Ab with the same antigen-specificity and substantially the same antigen-binding affinity or avidity, preferably at least 20% of the affinity or avidity of an Ab wherein the VL sequence is SEQ ID NO:1 and the VH sequence is SEQ ID NO:2. It is preferred that in this chimeric (or human) Ab, the three CDR regions of the VL chain are SEQ ID NO:3, 4 and 5 and the three CDR regions of the VH chain are SEQ ID NO:6, 7 and 8. [0066] Another preferred chimeric Ab (or human Ab) has a VL sequence SEQ ID NO:9 and a VH sequence SEQ ID NO:10 which are the amino acid sequences of mAb MNPR-102. The residues of these V regions that are not in the CDR regions may be varied, preferably as conservative substitutions, as long as the V region results in an Ab with the same antigen-specificity and substantially the same antigen-binding affinity or avidity, preferably at least 20% of the affinity or avidity of an Ab wherein the V_L sequence is SEQ ID NO:9 and the V_H sequence is SEQ ID NO:10. It is preferred that in this chimeric Ab, the three CDR regions of the V_L chain are SEQ ID NO:11, 12 and 13 and the three CDR regions of the V_H chain are SEQ ID NO:14, 15 and 16. [0067] Preferred nucleic acid molecules for use in constructing a chimeric Ab (or human Ab) of the disclosure are (i) a nucleic acid molecule with a coding sequence that encodes a V_L region with the sequence SEQ ID NO:1 and (ii) a nucleic acid molecule with a coding sequence that encodes a VH chain with the sequence SEQ ID NO:2. Also preferred is a nucleic acid molecule that encodes a VL region comprising the three CDRs SEQ ID 32591/70242 NO:3, 4 and 5 and a nucleic acid molecule that encodes a V_H region comprising the three CDRs SEQ ID NO:6, 7 and 8. [0068] Another set of preferred nucleic acid molecules for use in constructing a chimeric Ab (or human Ab) of the disclosure are (i) a nucleic acid molecule with a coding sequence that encodes a VL region with the sequence SEQ ID NO:9 and (ii) a nucleic acid molecule with a coding sequence that encodes a VH chain with the sequence SEQ ID NO:10. Also preferred is a nucleic acid molecule that encodes a VL region comprising the three CDRs SEQ ID NO:11, 12 and 13 and a nucleic acid molecule that encodes a VH region comprising the three CDRs SEQ ID NO:14, 15 and 16. [0069] Alternatively, the non-human Ab producing cell from which the V region of the Ab of the disclosure is derived may be a B lymphocyte obtained from the blood, spleen, lymph nodes or other tissue of an animal immunized with D2D3 of suPAR. The Ab-producing cell contributing the nucleotide sequences encoding the antigen-binding region of the chimeric Ab of the present disclosure may also be produced by transformation of a non-human, such as a primate, or a human cell. For example, a B lymphocyte which produces an Ab specific, e.g., uPA/uPAR or uPAR-integrin complex may be infected and transformed with a virus such as Epstein-Barr virus to yield an immortal Ab producing cell (Kozbor et al. Immunol. Today 4:72-79 (1983)). Alternatively, the B lymphocyte may be transformed by providing a transforming gene or transforming gene product, as is well-known in the art. Preferably, the antigen binding region will be of murine origin. In other embodiments, the antigen binding region may be derived from other animal species, in particular rodents such as rat or hamster. [0070] The murine or chimeric mAb of the present disclosure may be produced in large quantities by injecting hybridoma or transfectoma cells secreting the Ab into the peritoneal cavity of mice and, after appropriate time, harvesting the ascites fluid which contains a high titer of the mAb, and isolating the mAb therefrom. For such in vivo production of the mAb with a non-murine hybridoma (e.g., rat or human), hybridoma cells are preferably grown in irradiated or athymic nude mice. [0071] Alternatively, the antibodies may be produced by culturing hybridoma (or transfectoma) cells in vitro and isolating secreted mAb from the cell culture medium. [0072] Human genes which encode the constant C regions of the chimeric antibodies of the present disclosure may be derived from a human fetal liver library or from any human cell including those which express and produce human Igs. The human C_H region can be derived from any of the known classes or isotypes of human H chains, including γ, µ, α, δ or ε, and subtypes thereof, such as G1, G2, G3 and G4. Since the H chain isotype is responsible for the various effector functions of an Ab, the choice of CH region will be guided by the desired effector functions, such as complement fixation, or activity in Ab-dependent cellular cytotoxicity (ADCC). Preferably, the C_H region is derived from γ1 (IgG1), γ3 (IgG3), γ4 (IgG4), or µ (IgM). [0073] The human C_L region can be derived from either human L chain isotype, κ or λ. [0074] Genes encoding human Ig C regions are obtained from human cells by standard cloning techniques 32591/70242 (Sambrook, J. et al., Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Press, Cold Spring Harbor, NY (1989)). Human C region genes are readily available from known clones containing genes representing the two classes of L chains, the five classes of H chains and subclasses thereof. Chimeric Ab fragments, such as F(ab’)2 and Fab, can be prepared by designing a chimeric H chain gene which is appropriately truncated. For example, a chimeric gene encoding an H chain portion of an F(ab’)2 fragment would include DNA sequences encoding the CH1 domain and hinge region of the H chain, followed by a translational stop codon to yield the truncated molecule. [0075] Generally, the chimeric antibodies of the present disclosure are produced by cloning DNA segments encoding the H and L chain antigen-binding regions of a specific Ab of the disclosure, preferably non-human, and joining these DNA segments to DNA segments encoding human CH and CL regions, respectively, to produce chimeric Ig-encoding genes. [0076] Thus, in a preferred embodiment, a fused gene is created which comprises a first DNA segment that encodes at least the antigen-binding region of non-human origin, such as a functionally rearranged V region with joining (J) segment, linked to a second DNA segment encoding at least a part of a human C region. [0077] The DNA encoding the Ab-binding region may be genomic DNA or cDNA. A convenient alternative to the use of chromosomal gene fragments as the source of DNA encoding the murine V region antigen-binding segment is the use of cDNA for the construction of chimeric Ig genes, as reported by Liu et al. (Proc. Natl. Acad. Sci., USA 84:3439 (1987); J. Immunol.139:3521 (1987), which references are hereby incorporated by reference. The use of cDNA requires that gene expression elements appropriate for the host cell be combined with the gene in order to achieve synthesis of the desired protein. The use of cDNA sequences is advantageous over genomic sequences (which contain introns), in that cDNA sequences can be expressed in bacteria or other hosts which lack appropriate RNA splicing systems. Pharmaceutical Compositions and Their Administration [0078] The compounds that may be employed in the pharmaceutical compositions of the disclosure include all of the antibody radioisotope constructs described above, as well as the pharmaceutically acceptable salts of these compounds. Pharmaceutically acceptable acid addition salts of the compounds of the disclosure containing a basic group are formed where appropriate with strong or moderately strong, non-toxic, organic or inorganic acids by methods known to the art. Exemplary of the acid addition salts that are included in this disclosure are maleate, fumarate, lactate, oxalate, methanesulfonate, ethanesulfonate, benzenesulfonate, tartrate, citrate, hydrochloride, hydrobromide, sulfate, phosphate and nitrate salts. [0079] Pharmaceutically acceptable components for the purpose of radioprotection may be included in the pharmaceutical compositions described herein. Radioprotectants are compounds that can protect the composition from damage sustained due to the energy that is released during the radioactive decay of the composition. Suitable radioprotectants include but are not limited to gentisic acid, ascorbic acid, N-acetyl cysteine, additional antibody (e.g., unconjugated “cold” antibodies) or other targeting agent, human serum 32591/70242 albumin, and other compounds or materials known to those skilled in the art. [0080] Pharmaceutically acceptable base addition salts of antibody radioisotope constructs of the disclosure containing an acidic group are prepared by known methods from organic and inorganic bases and include, for example, nontoxic alkali metal and alkaline earth bases, such as calcium, sodium, potassium and ammonium hydroxide; and nontoxic organic bases such as triethylamine, butylamine, piperazine, and tri(hydroxymethyl)methylamine. [0081] The antibody radioisotope constructs of the disclosure, as well as the pharmaceutically acceptable salts thereof, may be incorporated into convenient dosage forms, such as capsules, impregnated wafers, tablets or injectable preparations. Solid or liquid pharmaceutically acceptable carriers may be employed. [0082] Solid carriers include starch, lactose, calcium sulfate dihydrate, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate and stearic acid. Liquid carriers include syrup, peanut oil, olive oil, saline, water, dextrose, glycerol and the like. Similarly, the carrier or diluent may include any prolonged release material, such as glyceryl monostearate or glyceryl distearate, alone or with a wax. When a liquid carrier is used, the preparation may be in the form of a syrup, elixir, emulsion, soft gelatin capsule, sterile injectable liquid (e.g., a solution), such as an ampoule, or an aqueous or nonaqueous liquid suspension. A summary of such pharmaceutical compositions may be found, for example, in Remington’s Pharmaceutical Sciences, Mack Publishing Company, Easton Pennsylvania (Gennaro 18th ed.1990). [0083] The pharmaceutical preparations are made following conventional techniques of pharmaceutical chemistry involving such steps as mixing, granulating and compressing, when necessary for tablet forms, or mixing, filling and dissolving the ingredients, as appropriate, to give the desired products for oral, parenteral, topical, transdermal, intravaginal, intrapenile, intranasal, intrabronchial, intracranial, intraocular, intraaural and rectal administration. The pharmaceutical compositions may also contain minor amounts of nontoxic auxiliary substances such as wetting or emulsifying agents, pH buffering agents and so forth. [0084] The present disclosure may be used in the diagnosis or treatment of any of a number of animal genera and species, and are equally applicable in the practice of human or veterinary medicine. Thus, the pharmaceutical compositions can be used to treat domestic and commercial animals, including birds and more preferably mammals, as well as humans. [0085] The term “systemic administration” refers to administration of a composition or agent such as the polypeptide, described herein, in a manner that results in the introduction of the composition into the subject’s circulatory system or otherwise permits its spread throughout the body, such as intravenous (i.v.) injection or infusion. “Regional” administration refers to administration into a specific, and somewhat more limited, anatomical space, such as intraperitoneal, intrathecal, subdural, or to a specific organ. Examples include intravaginal, intrapenile, intranasal, intrabronchial (or lung instillation), intracranial, intra-aural or intraocular. The term “local administration” refers to administration of a composition or drug into a limited, or circumscribed, anatomic space, subcutaneous (s.c.) injections, intramuscular (i.m.) injections. One of skill in the art would 32591/70242 understand that local administration or regional administration often also result in entry of a composition into the circulatory system, i.e.,, so that s.c. or i.m. are also routes for systemic administration. Injectables or infusible preparations can be prepared in conventional forms, either as solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection or infusion, or as emulsions. Though the preferred routes of administration are systemic, such as i.v., the pharmaceutical composition may be administered topically or transdermally, e.g., as an ointment, cream or gel; orally; rectally; e.g., as a suppository. [0086] Other pharmaceutically acceptable carriers for polypeptide compositions of the present disclosure are liposomes, pharmaceutical compositions in which the active protein is contained either dispersed or variously present in corpuscles consisting of aqueous concentric layers adherent to lipidic layers. The active polypeptide is preferably present in the aqueous layer and in the lipidic layer, inside or outside, or, in any event, in the non- homogeneous system generally known as a liposomic suspension. The hydrophobic layer, or lipidic layer, generally, but not exclusively, comprises phospholipids such as lecithin and sphingomyelin, steroids such as cholesterol, more or less ionic surface active substances such as dicetylphosphate, stearylamine or phosphatidic acid, and/or other materials of a hydrophobic nature. Those skilled in the art will appreciate other suitable embodiments of the present liposomal formulations. Imaging and Diagnostic Methods [0087] Also provided herein are methods of imaging a tissue in a patient, comprising (i) administering to the patient an effective amount of an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; and (ii) performing an imaging procedure to detect the antibody radioisotope construct in the tissue. [0088] In some cases, the radioisotope is ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ²¹²Pb, ¹⁶¹Tb, ¹⁷⁷Lu, or ²¹³Bi. In some cases, the radioisotope is ⁸⁹Zr. In some cases, the chelating linker comprises one squaramide moiety. In some cases, the chelating linker comprises more than one squaramide moiety. In some cases, the chelating linker comprises squaramide-modified diethylenetriamine pentaacetate (DTPA-Sq), squaramide-modified deferoxamine (DFO-Sq), squaramide-modified DFO* (DFO*-Sq), squaramide-modified dodecane tetraacetic acid (DOTA-Sq), or squaramide-modified Macropa (Macropa-Sq). In some cases, the chelating linker comprises DFO*-Sq. In some cases, the antibody moiety comprises an antibody, an antibody fragment, or a non-antibody uPAR- targeting protein. In some cases, the antibody moiety comprises an antibody or an antibody fragment. In some cases, the antibody moiety comprises an antibody. In some cases, the antibody moiety: i) has the heavy chain variable region CDR sequences set out in SEQ ID NOs: 6-8 and the light chain variable region sequences set out in SEQ ID NOs: 3-5; or ii) has the chain variable region CDR sequences set out in SEQ ID Nos: 14-16 and the light chain variable region 32591/70242 sequences set out in SEQ ID Nos: 11-13. In some cases, the antibody moiety: i) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 2 and the light chain variable region amino acid sequence set out in SEQ ID NO: 1; or ii) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 10 and the light chain variable region amino acid sequence set out in SEQ ID NO: 9. In some cases, the antibody moiety comprises MNPR-101 or MNPR-102. In some cases, the antibody moiety comprises MNPR-101. In some cases, the antibody radioisotope construct is MNPR-101-DFO*-Sq-⁸⁹Zr. [0089] In some cases, the tissue is soft tissue. In some cases, the tissue is inflamed tissue, cancer tissue, or healthy tissue. In some cases, the tissue is skeletal muscle, liver, pancreatic, colorectal, gastric, ovarian, breast, bladder, lung, bone marrow, or lymph node tissue. In some cases, the tissue is skeletal muscle. In some cases, the tissue is liver. In some cases, the tissue is bone marrow. In some cases, the tissue is cancer tissue. In some cases, the tissue comprises a tumor associated with one or more of lung cancer, ovarian cancer, prostate cancer, brain cancer, bladder cancer, head and neck cancer, pancreatic cancer, breast cancer, gastric, and colorectal cancer. [0090] In some cases, the imaging procedure comprises Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). In some cases, the imaging procedure comprises Single Photon Emission Computed Tomography (SPECT). In some cases, the imaging procedure comprises Positron Emission Tomography (PET). [0091] Further provided herein are methods of diagnosing a disease or disorder in a patient, comprising administering to the patient an effective amount of an antibody radioisotope construct disclosed herein, measuring the level of radiation in a first tissue and a second tissue, and diagnosing the disease or disorder if the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater. [0092] Also provided herein are methods of assessing effectiveness of uPAR-targeted therapy against a disease or disorder in a patient, comprising the steps of: (i) administering to the patient a uPAR-targeted therapy; (ii) administering to the patient an antibody radioisotope construct disclosed herein 2 to 52 weeks after administering the uPAR-targeted therapy; (iii) measuring the level of radiation in a first tissue and a second tissue 10 minutes to 30 days after administering the antibody radioisotope construct, and (iv) treating the disease or disorder with uPAR-targeted therapy if the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater. [0093] In various embodiments, the antibody radioisotope construct comprises: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties. In some embodiments, the antibody radioisotope construct is MNPR-101-DFO*-Sq-⁸⁹Zr. [0094] In some embodiments, the first tissue is tumor tissue. In some embodiments, the second tissue is blood, bone tissue (e.g., bone marrow), skeletal tissue, liver tissue, kidney tissue, or bladder tissue. In some 32591/70242 embodiments, the second tissue is liver tissue. In another embodiment, the second tissue is skeletal muscle. In another embodiment, the second tissue is blood (e.g., measured as a volume of interest in the descending aorta). In some embodiments, the first tissue is tumor tissue and the second tissue is liver tissue. In some embodiments, the first tissue is tumor tissue and the second tissue is skeletal muscle tissue. [0095] In some embodiments, the level of radiation is measured in the patient 10 minutes to 30 days after said administering. In some embodiments, the level of radiation is measured at other times after said administering, such as 10 minutes, or 2, 4, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, or 168 hours after said administering. In some embodiments, the radiation is measured as soon as 10 minutes to as long as 30 days after said administering, such as 10 minutes, 15 minutes, 30 minutes, or 45 minutes after said administering, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 hours after said administering, or 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, or 30 days after said administering. In some embodiments, the level of radiation is measured 2 weeks to 52 weeks after said administering. In some embodiments, the level of radiation is measured at other times after said administering, such as 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 12 weeks, 26 weeks, 38 weeks, or 52 weeks after said administering. In some embodiments, the level of radiation is measured 6 to 8 weeks after said administering. In some embodiments, the measuring comprises Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). In some embodiments, the ratio of the radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater, such as 1.5:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 15:1, 20:1, 25:1, 50:1, 75:1, 100:1, 200:1, 500:1, 1,000:1, or greater. In some cases, the ratio of radiation measured in the first tissue compared to the second tissue is 2:1 or greater. In some cases, the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater, and the second tissue is liver tissue. In some cases, the ratio of radiation measured in the first tissue compared to the second tissue is 2:1 or greater, and the second tissue is skeletal muscle tissue. [0096] In some embodiments directed to assessing the effectiveness of a uPAR therapy, a diagnostic administration of an antibody radioisotope construct or drug product disclosed herein is performed from 2 weeks to 52 weeks after a therapeutic administration of a uPAR therapy. In some embodiments, the diagnostic administration occurs at other times after the therapeutic administration, such as 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 12 weeks, 26 weeks, 38 weeks, or 52 weeks after said administering. In some embodiments, the level of radiation is measured 6 to 8 weeks after said therapeutic administration. Therapeutic Methods [0097] Further provided herein are methods of treating a disease or disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of an antibody radioisotope construct disclosed herein. In various embodiments, the antibody radioisotope construct comprises: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties. In some embodiments, the antibody radioisotope construct is MNPR-101-DFO*-Sq-⁸⁹Zr. 32591/70242 [0098] In some cases, administering an antibody radioisotope construct comprises the steps of: (a) administering a mass dose of the antibody radioisotope construct; (b) assessing one or more pharmacokinetic properties of the antibody radioisotope construct; and (c) adjusting a subsequent mass dose of the antibody radioisotope construct or a different (e.g. therapeutic) radioisotope construct based on the assessing in step (b). In some cases, the assessing step (b) comprises (i) assessing one or more pharmacokinetic parameters in the patient after administration of the antibody radioisotope construct; and (ii) determining whether a subsequent dose of the antibody radioisotope construct or a different radioisotope construct should maintain, reduce, or increase the total antibody dose for the patient; and the adjusting step (c) comprises maintaining, reducing, or increasing the total antibody dose for the patient based on the determining step (ii). [0099] In some cases, administering an antibody radioisotope construct comprises the steps of: (a) administering a mass dose of the antibody radioisotope construct; (b) assessing one or more pharmacokinetic properties of the antibody radioisotope construct; and (c) adjusting a subsequent mass dose of the antibody radioisotope construct based on the assessing in step (b). In some cases, the assessing step (b) comprises (i) assessing one or more pharmacokinetic parameters in the patient after administration of the antibody radioisotope construct; and (ii) determining whether a subsequent dose of the antibody radioisotope construct should maintain, reduce, or increase the total antibody dose for the patient; and the adjusting step (c) comprises maintaining, reducing, or increasing the total antibody dose for the patient based on the determining step (ii). [00100] In some embodiments, the disease or disorder is cancer. In some embodiments, the cancer is one or more of lung cancer, ovarian cancer, prostate cancer, brain cancer, bladder cancer, head and neck cancer, pancreatic cancer, breast cancer, gastric, or colorectal cancer. [00101] Also provided herein are methods of treating cancer in a patient in need thereof, comprising (i) diagnosing cancer in a patient by administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; (ii) diagnosing the patient with cancer if the ratio of radiation measured in a first tissue compared to a second tissue is 1.5:1 or greater, and (iii) administering to the patient a therapeutically-effective amount of a cancer therapeutic. In some cases, the ratio of radiation measured in the first tissue compared to the second tissue is 2:1 or greater. In some cases, the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater, and the second 32591/70242 tissue is liver tissue. In some cases, the ratio of radiation measured in the first tissue compared to the second tissue is 2:1 or greater, and the second tissue is skeletal muscle tissue. [00102] In various embodiments, the diagnosing comprises measuring the level of radiation in a first tissue and a second tissue, measured in the patient 10 minutes to 30 days after said administering, said measuring comprising Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET); and diagnosing the cancer if the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater. [00103] In various embodiments, the cancer therapeutic is a chemotherapeutic regimen, radiation therapy, antibody therapy, cell therapy, bone marrow transplant surgery, other known cancer therapy, or a combination thereof. [00104] In various embodiments, the cancer is metastatic cancer. [00105] In another embodiment, provided are methods of estimating the radiation dose received by a patient from an antibody radioisotope construct disclosed herein in a patient, comprising administering to the patient a sufficient amount of an antibody radioisotope construct disclosed herein, measuring the level of radiation in one or more organs (including but not limited to the liver, heart, lungs, kidneys, and bone marrow) and/or the blood at one or more timepoints, and calculating the effective absorbed dose for ⁸⁹Zr and optionally estimating the projected dose for a different antibody radioisotope construct, including but not limited to the projected therapeutic dose of a therapeutic antibody radioisotope construct. [00106] Therapeutic compositions may comprise, in addition to the antibody radioisotope constructs, one or more additional drugs, such as DNA-damage repair inhibitors, immune checkpoint inhibitors, growth factors, immune system modulators, radiosensitizers, CAR T-cell therapies, and chemotherapeutic agents. In fact, pharmaceutical compositions comprising any known therapeutic in combination with the antibody radioisotope constructs disclosed herein are within the scope of the disclosure. The pharmaceutical composition may also comprise one or more other medicaments to treat additional symptoms for which the target patients are at risk, for example, anti-infectives. [00107] The therapeutic dosage administered is an amount which is therapeutically effective, as is known to or readily ascertainable by those skilled in the art. The dose is also dependent upon the age, health, and weight of the recipient, kind of concurrent treatment(s), if any, the frequency of treatment, and the nature of the effect desired, such as, for example, anti-cancer effect. Drug Products [00108] Also provided herein are drug products comprising an antibody radioisotope disclosed herein, one or more antibodies, and a pharmaceutically acceptable excipient. In some cases, the antibody radioisotope construct comprises MNPR-101-DFO*-Sq-⁸⁹Zr. In some cases, the antibody radioisotope construct comprises a fragment of MNPR-101. In some cases, the antibody radioisotope construct comprises a linker that is not DFO*. 32591/70242 In some cases, the antibody radioisotope construct comprises a metal that is not ⁸⁹Zr. In some cases, the one or more antibodies comprise MNPR-101. [00109] In various embodiments, the drug products comprise one or more radioprotectants, a pharmaceutically acceptable carrier, or a combination thereof. [00110] In some cases, the drug products comprise one or more radioprotectants. In some cases, the one or more radioprotectants comprise ascorbic acid, gentisic acid, N-acetyl cysteine, human serum albumin, one or more unconjugated “cold” antibodies, or a combination thereof. [00111] In some cases, the drug products comprise one or more unconjugated “cold” antibodies. Cold antibodies are described in more detail in the section “Cold Antibodies” below. In some cases, the one or more unconjugated “cold” antibodies and the antibody of the antibody radioisotope construct are the same. In some cases, the one or more unconjugated “cold” antibodies and the antibody of the antibody radioisotope construct are different. [00112] In some cases, the drug products have a defined total antibody mass dose. In some cases, the total antibody mass dose is about 1 mg to about 80 mg. In some cases, the total antibody mass dose is about 2 mg to about 30 mg. In some cases, the total antibody mass dose is about 4.5 mg to about 20 mg. In some cases, the total antibody mass dose is about 10 mg. [00113] In some cases, the drug products have a defined conjugate to antibody ratio (CAR) with respect to the sample of interest. In some cases, the conjugate to antibody (CAR) ratio is less than 1. Cold Antibodies [00114] In some embodiments, the antibody radioisotope constructs of the disclosure are provided with a “hot” kit and a “cold” kit. A “cold” kit comprises the mAb conjugated to a chelator that is combined with the “hot” kit, a pharmaceutically acceptable formulation of the radionuclide just prior to administration to a patient for diagnosis or therapy. [00115] Targeted antigens, such as uPAR, often have low-level expression in normal tissue (Zhai et al. Journal of Translational Medicine (2022) 20:135). At very low doses of antibody, this normal tissue expression of the target captures a significant portion of the circulating antibody, increasing background uptake, accelerating clearance, and reducing the antibody available to the tumor in an effect known as Target-Mediated Drug Distribution (TMDD) (Ponte et al., Mol Cancer Ther 2021;20:203–12). In a study by Cao et al, the modeled and observed impact of TMDD is shown for several antibodies, and examples of concentration-dependent clearance profile for an antibody are shown (Cao et al, J Pharmacokinet Pharmacodyn.2014; 41(4): 375–387). [00116] The addition of cold antibody allows more radiolabeled antibody to reach the tumor by saturating the low-level expression in normal tissue without saturating the tumor (where target expression is much higher). The result is improved image quality via higher tumor-to-background ratio and reduced off-target uptake as illustrated in a study by Pandit-Taskar (Pandit-Taskar et al., J Nuc Med June 2023;64 supp1:P630 SNMMI 2023 poster 32591/70242 presentation). Because the amount of cold antibody that is added can determine the distribution and pharmacokinetics of the diagnostic or therapeutic agent, measuring the amount of circulating antibody via a quantitative or qualitative imaging assessment, for example a measurement of activity concentration in the aortic blood pool, heart contents, or red marrow, measured on a quantitative PET or quantitative SPECT scan, or via a blood draw assessed with a test such as HPLC, ELISA, radioactivity counts, or other tests known to those skilled in the art, may be used to determine whether the administered diagnostic dose of antibody contains the optimal amount of cold antibody. If the circulating antibody is higher or lower than the ideal level, the amount of cold antibody can be tailored in a future administration of a pharmaceutically suitable construct. A cold antibody may be used with the antibody radioisotope constructs described herein and drug products comprising the same to improve biodistribution of the antibody radioisotope constructs. In other cases, a cold antibody may play the role of a radioprotectant when administered with the antibody radioisotope constructs described herein and drug products comprising the same. [00117] Multiple published studies exploring cold antibody dosing with radiopharmaceuticals have similarly demonstrated that cold antibody increases image quality, with the optimal dosing generally falling in the 2 - 80mg range. (Pandit-Taskar N et al, J Nucl Med.2024 Jul 1;65(7):1051-1056; Morris MJ et al, Clin Cancer Res.2007 May 1;13(9):2707-13.) [00118] Because the antibody mass dose for a preferred embodiment of antibody radioisotope construct disclosed herein (e.g., MNPR-101-DFO*-Sq-⁸⁹Zr) described herein is in the range of 1-2 mg in total for a patient dose (or the equivalent of 0.017 – 0.033 mg/kg for a 60 kg patient), this extremely small dose of antibody is susceptible to TMDD. The administration of additional cold (also referred to as “unconjugated” or “naked”) antibody (e.g., MNPR-101) to a patient can be used to counteract the effects of TMDD, which includes the rapid sequestering of the antibody radioisotope construct (e.g., MNPR-101-DFO*-Sq-⁸⁹Zr) by low-level expression of uPAR in normal tissue and the associated suboptimal tumor uptake. The cold antibody can be administered prior to, concurrent with (including as part of the drug product formulation), or after injection of the antibody radioisotope construct (e.g., MNPR-101-DFO*-Sq-⁸⁹Zr) imaging agent. The amount of cold antibody used for a patient can range from about 1 mg to 200 mg such that the total antibody mass dose (the sum of the antibody radioisotope construct mass and cold antibody mass) is preferably 2 mg to 80 mg, more preferably 4.5 mg to 30 mg, and most preferable 10 mg to 20 mg. [00119] The cold antibody can be added in formulation of the final drug product such that the total antibody mass dose (the sum of the antibody radioisotope construct mass dose and cold antibody mass dose) in the drug product is preferably 2 mg to 80 mg, more preferably 4.5 mg to 30 mg, and most preferable 10 mg to 20 mg. The addition of cold antibody will reduce the average conjugate-to-antibody (CAR) ratio in the final drug product. For example, in one embodiment, approximately 8 mg of cold antibody of MNPR-101 may be added to approximately 2 mg of MNPR-101-DFO*-Sq-⁸⁹Zr having a CAR of 1.32 described herein to create a total antibody mass dose of 10 mg with a resulting proportional decrease in the conjugate-to-antibody ratio (CAR) to 0.264 in the final drug product. 32591/70242 [00120] The drug product may include an antibody radioisotope construct disclosed herein (e.g., MNPR-101- DFO*-Sq-⁸⁹Zr) including other radioisotopes and linkers described herein, cold antibody (e.g., MNPR-101), a pharmaceutically acceptable carrier or buffer for sterile injection such as sterile saline for example, and optionally at least one radioprotectant including ascorbic acid, gentisic acid, N-acetyl cysteine, cold antibody, human serum albumin, and others known to those skilled in the art. These radioprotectants can be added in concentrations of 0.1-100 mg/ml gentisic acid, 0.1-100 mg/ml N-acetyl cysteine, and 0.1-100 mg/ml sodium ascorbate. These radioprotectants may be added via dilution from 10X concentrated stock solutions. The inclusion of cold antibody in the final antibody radioisotope construct (e.g., MNPR-101-DFO*-Sq-⁸⁹Zr) drug product vial simplifies the administration of cold antibody with a single patient injection of the drug. The inclusion of cold antibody in the product vial also serves to protect the radiolabeled antibody from radiation damage thereby improving the overall stability of the antibody radioisotope construct. [00121] The cold antibody may also be included in a kit comprising the final drug product vial or other acceptable container of the formulation for antibody radioisotope constructs described herein (e.g., MNPR-101- DFO*-Sq-⁸⁹Zr) or other antibody constructs (e.g., MNPR-101 compounds) described herein in an appropriately shielded container, a vial or other acceptable container of cold antibody (e.g., MNPR-101 antibody) in a sterile, pharmaceutically acceptable carrier for injection such as saline, and optionally, one or more syringes and syringe filters for extraction and injection. [00122] In various embodiments, the disease or disorder is cancer as described herein. In various embodiments, the diagnosing detects cancer that has metastasized. Kits [00123] Also provided herein are kits comprising a) an antibody radioisotope construct or drug product disclosed herein, b) a drug product comprising one or more antibodies, and c) optionally one or more syringes, one or more filter needles, and/or one or more needles for IV injection. In some cases, the antibody radioisotope construct comprises MNPR-101-DFO*-Sq-⁸⁹Zr or the drug product comprises a MNPR-101-DFO*-Sq-⁸⁹Zr drug product. In some cases, the antibody radioisotope construct comprises MNPR-101-DFO*-Sq-⁸⁹Zr. In some cases, the drug product comprises a MNPR-101-DFO*-Sq-⁸⁹Zr drug product. In some cases, the drug product comprises one or more antibodies. In some cases, the drug product comprises a MNPR-101 drug product. In some cases, the kit further comprises one or more cold antibodies. In some cases, the kit further comprises one or more syringes, one or more filter needles, and/or one or more needles for IV injection. Other Embodiments [00124] It is to be understood that while the disclosure is read in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the disclosure, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims. 32591/70242 EXAMPLES [00125] The following examples are provided for illustration and are not intended to limit the scope of the disclosure. Example 1: Synthesis and Characterization of Antibody DFO Conjugates [00126] MNPR-101-DFO-NCS-⁸⁹Zr was synthesized using a 1:5 stochiometric ratio of MNPR-101 to p-SCN- Bz-DFO using a process consistent with Hernandez et al., Mol Pharm.2016; 13(7): 2563-2570. Notably, the synthetic process included purification steps by PD-10 column following both conjugation and chelation to remove unconjugated DFO or ⁸⁹Zr-DFO as well as any free ⁸⁹Zr. Stability testing of MNPR-101-DFO-NCS-⁸⁹Zr was performed using thin layer chromatography (TLC) and radio high performance liquid chromatography (rad- HPLC) after storage in saline at 2-8 °C and serum incubated at 37°C at different timepoints. The results are provided in Table 4, and show only minor degradation of the MNPR-101-DFO-NCS-⁸⁹Zr construct in vitro over 7 days. TABLE 4. Thin layer chromatography (TLC) data of MNPR-101-DFO-NCS-⁸⁹Zr in saline and serum [00127] However, when in vivo experiments were performed with MNPR-101-DFO-NCS-⁸⁹Zr in tumor-free mice as described in Example 3, there was a significant and unexpected loss of activity from mice within the 1^st day of injection, which affected overall biodistribution and tumor uptake. Early imaging scans at 6h showed accumulation in the bladder (See FIG 7 at 6h bladder), and high radioactivity measured in the urine and feces excretions as well as sacrificial whole-body dosimetry (see FIG 5 with whole-body retention) confirmed rapid and substantial loss of approximately 50% of the ⁸⁹Zr activity within the first 24-hours. Other than performing the experiment in live mice, by injecting the drug and checking for retention/clearance levels of the drug, there was no suitable analytical method for identifying the stability issue with DFO-NCS. [00128] Therefore, it was decided to replace the NCS thiourea bond to MNPR-101 with a more stable bond such as a squaramide structure that exclusively binds to primary amines (e.g. lysine). This is far more repeatable for manufacturing than the NCS structure since the nature of most manufacturing process makes it challenging to determine and maintain pH in the narrow range needed for optimal lysine selectivity, and even with such pH, some cysteine bonding remains. Without wishing to be bound by any particular theory, it is also believed that thiourea bonds formed by the NCS linker are more hydrophobic than the bonds formed by the squaramide 32591/70242 linkers, which can in some cases lead to unwanted aggregation of the NCS-linked antibodies. Example 2: Synthesis and Characterization of Antibody DFO* Conjugates [00129] Instead of the p-SCN-Bz-DFO used in Example 1, an analogue of DFO with a squaramide linker, deferoxamine*-squaramide (DFO*-squaramide or DFO*-Sq, structure shown in FIG 2), was selected. The DFO*- Sq chelator was selected because of its selectivity to lysine, reported improved chelation of ⁸⁹Zr, and reduced bone uptake. Other suitable chelators, including without limitation DFO, oxoDFO*, and DOTA (e.g., DOTA with a squaramide linker as previously described in DOTA-Sq Heskamp et al., Bioconjug Chem.2017; 28(9): 2211- 2223) can be used as described herein. [00130] The preparation of MNPR-101 with DFO*-Sq (FIG 3) was modified from Rudd et al., Chem. Commun. 2016; 52: 11889-11892). 10 mg of MNPR-101 (initially in 250 mM phosphate buffer in 150mM sodium chloride, pH 7.4) was added to a 0.4 M borate buffer (initially at pH~9). The pH of the reaction was adjusted to 9 with 0.1 M Na2CO3. Approximately 5 equivalents of DFO*-Sq (ABX) in DMSO was added to the MNPR-101 solution, and the reaction mixture was incubated overnight at room temperature. MNPR-101-DFO*-Sq conjugate was then purified using a PD-10 column with 0.25 M sodium acetate buffer pH 5.5. Antibody concentration was determined and number of chelates per antibody were determined by size exclusion-HPLC. Assay results showed that the yield of the isolated conjugate was ~ 70% with 1.3 DFO*-Sq per antibody molecule. [00131] Immunoaffinity of the resulting MNPR-101-DFO*-Sq conjugate (prepared at 5 equivalents of DFO*-Sq to MNPR-101) was evaluated using an ELISA method and uPAR protein. The results in FIG 4 showed that the relative potency of MNPR-101-DFO*-Sq was estimated to be ~76% compared to MNPR-101. HPLC analysis showed an average conjugate-to-antibody ratio (CAR) of 1.32. Results were similar to the previous MNPR-101- DFO-NCS immunoaffinity study referenced in Fig.5 of Mazar et al in U.S.2023-0338590 A1 which showed that at 4:1 DFO-NCS to MNPR-101 stochiometric ratio, the resulting CAR was 1.9, and the relative potency of MNPR- 101-DFO-NCS was 66%. The conjugate-to-antibody ratio (CAR) may be reduced to less than 1 by reducing the ratio of molar equivalents of DFO*-Sq conjugate to MNPR-101 (e.g., from 5 molar equivalents to 1 molar equivalent or less of DFO*-Sq) during preparation of the conjugate. Alternatively, cold (unconjugated) MNPR- 101 antibody may be added to the MNPR-101-DFO*-Sq conjugate to reduce the CAR in the final drug product. [00132] Radiolabeling and purification to obtain MNPR-101-DFO*-Sq^-89Zr were performed in the same way as for the other radioimmunoconjugates (Vosjan et al., Nat Protoc.2010; 5: 739–743). 5.5 mCi of ⁸⁹Zr oxalate solution was charged in a vial. 0.5 M HEPES pH 7.2 was added, followed by about 2 mg of the conjugate. Subsequently another 0.5 M HEPES solution was added to the reaction mixture, and the pH was adjusted to 7.2 using 2 M Na₂CO₃. The reaction mixture was incubated for 1 hour at room temperature. The zirconium-labeled MNPR-101-DFO*-Sq conjugate was then purified using a PD-10 column with 0.25 M sodium acetate buffer at pH 5.5 and with 5mg/mL gentisic acid. The concentration of labeled conjugate was determined by using the size exclusion HPLC. [00133] In some examples, the labeled conjugate is then combined with desired amount of naked antibody 32591/70242 and saline to make the final formulation that has a total mass dose of antibody ranging from ~4.5 to 80 mg. Addition of this cold antibody into the radiolabeled conjugate promotes selective tumor uptake relative to healthy tissue various mechanisms of active like out-competing labeled antibody to bind to sinks, promoting intra tumoral distribution of the labeled antibody and blocking sites of non-specific binding. [00134] MNPR-101-DFO*-Sq-⁸⁹Zr was tested for stability using HPLC for chemical and radiopurity at T0 and day 5 after storage of the drug at 2-8 °C in saline. The construct was found to be stable for a period of at least 7 days after manufacturing with a purity of >90% when stored at 2-8 °C. The construct was also tested at an accelerated storage condition of room temperature for 24 hours, after which it demonstrated >90% purity. Data from this stability assay are presented in Table 5: TABLE 5. HPLC results showing chemical and radiopurity of MNPR-101-DFO*-Sq at T0 and after storage at 2- 8°C for 5 days. Example 3: in vivo Stability of Antibody DFO* Conjugates [00135] MNRP-101-DFO*-Sq was injected into mice (tumor-free) to evaluate the in vivo stability and dosimetry of MNPR-101-DFO*-Sq-⁸⁹Zr. Whole-body retention of MNPR-101-DFO-NCS-⁸⁹Zr and MNPR-101-DFO*-Sq-⁸⁹Zr in the mouse body was estimated using naïve immunocompromised mice administered around 210 µCi of MNPR-101-DFO-NCS-⁸⁹Zr and 100 µCi of MNPR-101-DFO*-Sq-⁸⁹Zr, which were sacrificed at 3 hours, 1 day, 2 days (MNPR-101-DFO-NCS-⁸⁹Zr group only), 5 days, 7 days (MNRP-101-DFO*-Sq-⁸⁹Zr group only), and 15 days post-injection. Whole body retention of radioactivity was measured using a well counter. Results showed that approximately 50% of the MNPR-101-DFO-NCS-⁸⁹Zr activity was cleared within 24 hours of administration while MNPR-101-DFO*-Sq-⁸⁹Zr showed less than 10% clearance, and the level of circulating activity of MNPR- 101-DFO*-Sq-⁸⁹Zr was significantly higher at all timepoints (FIGs 5 and 6). Imaging at 3 hours also confirmed the absence of significant activity in the kidneys or bladder, FIG 7. [00136] Naïve mice (with no tumors) were administered MNPR-101-DFO-NCS-⁸⁹Zr at ~260 µCi and MNPR- 101-DFO*-Sq-⁸⁹Zr at ~100 µCi and imaged using PET at early time points, 6 hours and 3 hours after injection, respectively. The MNPR-101-DFO-NCS-⁸⁹Zr drug showed signs of excretion through bladder at this early time point, which is unusual for antibody-based drugs. [00137] Example 4: in vivo Tumor Uptake of Antibody-DFO and Antibody-DFO* Conjugates 32591/70242 [00138] Tumor-bearing immunocompromised mice were dosed with either MNPR-101-DFO-NCS-⁸⁹Zr or MNPR-101-DFO*-Sq-⁸⁹Zr, and the uptake and stability of the conjugates were evaluated using imaging methods. [00139] A pancreatic cancer cell line, MIA PaCa-2, also known to express uPAR as reported in Gorantla et al., Mol Cancer Res 2011; 9(4): 377-89, was used to develop a xenograft mouse model in immunocompromised mice. From 80 - 85% confluent culture, 2 - 5 x 10⁶ cells were suspended in 100 µl of 1:1 mixture of PBS and Matrigel® (Corning) and subcutaneously injected into the lower right flank of 4-6 -week-old female athymic nude mice. [00140] Mice with tumor volume between 100 - 200 mm³ were injected intravenously (iv) in the lateral tail vein with 210 - 268 µCi of MNPR-101-DFO-NCS-⁸⁹Zr. Mice with tumor volume between 500 - 1000 mm³ were injected intravenously (iv) in the lateral tail vein with 247 - 261 µCi of MNPR-101-DFO*-Sq-⁸⁹Zr. [00141] PET images were acquired using a micro-PET/CT scanner. Before each PET scan, mice were anesthetized in an induction chamber using 4% gas isoflurane anesthesia, and subsequently placed in the prone position in the scanner and maintained with 2% isoflurane. Sequential list mode PET scans of 20-40 million coincidence events per mouse (time window: 3.432 ns; energy window: 350-650 keV) were acquired at various time points after administration of the radiodiagnostic agent. The PET images were reconstructed using three- dimensional ordered subset expectation maximization/maximum a posterior (OSEM3D/MAP) reconstruction (18 iterations, 16 subsets) with a 128 x 128 image matrix resulting in ~0.8mm cubic voxels. Quantitative region-of- interest analysis (ROI) was then performed. [00142] The results (FIG.8) showed a surprising and significant improvement in tumor uptake of MNPR-101- DFO*-Sq-⁸⁹Zr relative to MNPR-101-DFO-NCS-⁸⁹Zr (note the difference in scale) as well as significantly improved tumor-to-liver and tumor-to-skeletal muscle ratios. Without wishing to be bound by any particular theory, increased tumor uptake is likely due to the increased bioavailability of MNPR-101-DFO*-Sq-⁸⁹Zr in circulation. [00143] Example 5: Improved Biodistribution in Patient Images of MNPR-101-DFO*-89Zr with optimized mass dose [00144] Patients with the same type of advanced rare adenocarcinoma were dosed with different mass doses of MNPR-101-DFO*-89Zr. The patients then underwent serial PET/CT scans to detect the distribution of MNPR- 101-DFO*-89Zr in healthy tissues and tumor tissues over the course of 1 week. As shown in FIG.9, the patient that received a higher mass dose showed more favorable biodistribution, including lower uptake in healthy organs and higher uptake in tumors over time. [00145] Example 6: Patient evidence of improved stability of MNPR-101-DFO*-89Zr due to squaramide linker [00146] A patient with metastatic ovarian cancer was dosed with MNPR-101-DFO*-89Zr. The patients then underwent serial PET/CT scans to detect the distribution of MNPR-101-DFO*-89Zr in healthy tissues and tumor tissues over the course of 1 week. As shown in FIG.10, the images show no rapid clearance of the antibody 32591/70242 through the kidneys and bladder and durable uptake in tumor tissues. This demonstrates that the squaramide linker of MNPR-101-DFO*-89Zr shows optimized stability for use as a diagnostic agent in humans.

Claims

32591/70242 We Claim: 1. A method of imaging a tissue in a patient, comprising (i) administering to the patient an effective amount of an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; and (ii) performing an imaging procedure to detect the antibody radioisotope construct in the tissue. 2. The method of claim 1, wherein the radioisotope is ⁴⁷Sc, ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ⁹⁰Y, ¹⁰⁹Pd, 1⁸⁶Re, ¹⁸⁸Re, ¹⁹⁹Au, ²¹¹At, ²¹²Pb, ²¹³Bi, ²²³Ra, ²²⁷Th, ¹⁶¹Tb, ¹⁷⁷Lu, or ²²⁵Ac. 3. The method of claim 1 or 2, wherein the radioisotope is ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ²¹²Pb, 1⁶¹Tb, ¹⁷⁷Lu, or ²¹³Bi. 4. The method of any one of claims 1 to 3, wherein the radioisotope is ⁸⁹Zr. 5. The method of any one of claims 1 to 4, wherein the chelating linker comprises one squaramide moiety. 6. The method of any one of claims 1 to 5, wherein the chelating linker comprises squaramide- modified diethylenetriamine pentaacetate (DTPA-Sq), squaramide-modified deferoxamine (DFO-Sq), squaramide-modified DFO* (DFO*-Sq), squaramide-modified dodecane tetraacetic acid (DOTA-Sq), or squaramide-modified Macropa (Macropa-Sq). 7. The method of any one of claims 1 to 6, wherein the chelating linker comprises DFO*-Sq. 8. The method of any one of claims 1 to 7, wherein the antibody moiety comprises an antibody, an antibody fragment, or a non-antibody uPAR-targeting protein. 9. The method of any one of claims 1 to 8, wherein the antibody moiety: i) has the heavy chain variable region CDR sequences set out in SEQ ID NOs: 6-8 and the light chain variable region sequences set out in SEQ ID NOs: 3-5; or ii) has the chain variable region CDR sequences set out in SEQ ID Nos: 14-16 and the light chain variable region sequences set out in SEQ ID Nos: 11-13. 10. The method of any one of claims 1 to 8, wherein the antibody moiety: i) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 2 and the light chain variable region amino acid sequence set out in SEQ ID NO: 1; or 32591/70242 ii) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 10 and the light chain variable region amino acid sequence set out in SEQ ID NO: 9. 11. The method of any one of claims 1 to 10, wherein the antibody moiety comprises MNPR-101 or MNPR-102. 12. The method of claim 11, wherein the antibody moiety comprises MNPR-101. 13. The method of any one of claims 1 to 12, wherein the antibody radioisotope construct is MNPR-101-DFO*-Sq-⁸⁹Zr. 14. The method of any one of claims 1 to 13, wherein the tissue is soft tissue. 15. The method of claim 14, wherein the tissue is pancreatic, colorectal, gastric, ovarian, breast, bladder, lung, bone marrow, or lymph node tissue. 16. The method of claim 14 or 15, wherein the tissue is bone marrow. 17. The method of any one of claims 1 to 16, wherein the tissue is cancer tissue. 18. The method of claim 17, wherein the cancer tissue comprises a tumor associated with one or more of lung cancer, ovarian cancer, prostate cancer, brain cancer, bladder cancer, head and neck cancer, pancreatic cancer, breast cancer, gastric, and colorectal cancer. 19. The method of any one of claims 1 to 18, wherein the administering comprises administering the antibody radioisotope construct to the patient via injection. 20. The method of claim 19, further comprising administering to the patient one or more antibodies. 21. The method of claim 20, wherein the one or more antibodies comprise unconjugated “cold” antibodies. 22. The method of claim 20 or 21, wherein the one or more antibodies comprise MNPR-101. 23. The method of any one of claims 1 to 22, wherein the antibody radioisotope construct has a conjugate-to-antibody ratio (CAR) of less than 1. 24. The method of any one of claims 1 to 23, wherein the antibody radioisotope construct has a conjugate-to-antibody ratio (CAR) of between 0.1 and 1. 32591/70242 25. The method of any one of claims 1 to 24, wherein the imaging procedure comprises Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). 26. A method of diagnosing a disease or disorder in a patient, comprising the steps of: (i) administering to the patient an effective amount of an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; (ii) measuring the level of radiation in a first tissue and a second tissue, measured in the patient 10 minutes to 30 days after said administering, said measuring comprising Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET); and (iii) diagnosing the disease or disorder if the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater. 27. A method of assessing effectiveness of uPAR-targeted therapy against a disease or disorder in a patient, comprising the steps of: (i) administering to the patient a uPAR-targeted therapy; (ii) administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties and wherein administering the antibody radioisotope construct occurs 2 to 52 weeks after administering the uPAR-targeted therapy; (iii) measuring the level of radiation in a first tissue and a second tissue, measured in the patient 10 minutes to 30 days after administering the antibody radioisotope construct, said measuring comprising Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET); and (iv) treating the disease or disorder with uPAR-targeted therapy if the ratio of radiation measured in the first tissue compared to the second tissue is 1.5:1 or greater. 28. The method of claim 26 or 27, wherein the ratio of radiation measured in the first tissue compared to the second tissue is 2:1 or greater. 29. The method of any one of claims 26 to 28, wherein the radioisotope is ⁴⁷Sc, ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ⁹⁰Y, ¹⁰⁹Pd, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁹⁹Au, ²¹¹At, ²¹²Pb, ²¹³Bi, ²²³Ra, ²²⁷Th, ¹⁶¹Tb, ¹⁷⁷Lu, or ²²⁵Ac. 30. The method of any one of claims 26 to 29, wherein the radioisotope is ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ²¹²Pb, ¹⁶¹Tb, ¹⁷⁷Lu, or ²¹³Bi. 32591/70242 31. The method of any one of claims 26 to 30, wherein the radioisotope is ⁸⁹Zr. 32. The method of any one of claims 26 to 31, wherein the chelating linker comprises one squaramide moiety. 33. The method of any one of claims 26 to 32, wherein the chelating linker comprises squaramide- modified diethylenetriamine pentaacetate (DTPA-Sq), squaramide-modified deferoxamine (DFO-Sq), squaramide-modified DFO* (DFO*-Sq), squaramide-modified dodecane tetraacetic acid (DOTA-Sq), or squaramide-modified Macropa (Macropa-Sq). 34. The method of any one of claims 26 to 33, wherein the chelating linker comprises DFO*-Sq. 35. The method of any one of claims 26 to 34, wherein the antibody moiety comprises an antibody, an antibody fragment, or a non-antibody uPAR-targeting protein. 36. The method of any one of claims 26 to 35, wherein the antibody moiety: i) has the heavy chain variable region CDR sequences set out in SEQ ID Nos: 6-8 and the light chain variable region sequences set out in SEQ ID Nos: 3-5; or ii) has the chain variable region CDR sequences set out in SEQ ID Nos: 14-16 and the light chain variable region sequences set out in SEQ ID Nos: 11-13. 37. The method of any one of claims 26 to 36, wherein the antibody moiety: i) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 2 and the light chain variable region amino acid sequence set out in SEQ ID NO: 1; or ii) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 10 and the light chain variable region amino acid sequence set out in SEQ ID NO: 9. 38. The method of any one of claims 26 to 37, wherein the antibody moiety comprises MNPR-101 or MNPR-102. 39. The method of claim 38, wherein the antibody moiety comprises MNPR-101. 40. The method of any one of claims 26 to 39, wherein the antibody radioisotope construct is MNPR-101-DFO*-Sq-⁸⁹Zr. 41. The method of any one of claims 26 to 40, wherein the disease or disorder is cancer. 42. The method of claim 41, wherein the cancer is one or more of lung cancer, ovarian cancer, prostate cancer, brain cancer, bladder cancer, head and neck cancer, pancreatic cancer, breast cancer, gastric, or colorectal cancer. 32591/70242 43. The method of any one of claims 26 to 42, wherein the first tissue is tumor tissue. 44. The method of any one of claims 26 to 43, wherein the second tissue is liver tissue, skeletal muscle tissue, or blood. 45. The method of any one of claims 26 to 44, wherein the measuring comprises Positron Emission Tomography (PET). 46. The method of any one of claims 26 to 45, wherein the measuring occurs 6 to 8 weeks after said administering. 47. An antibody radioisotope construct comprising: one or more radioisotopes; one or more chelating linkers; and an antibody moiety selected from MNPR-101, MNPR-102, and fragments thereof, wherein the one or more chelating linkers are attached to the antibody moiety through one or more linking moieties. 48. The antibody radioisotope construct of claim 47, wherein the one or more radioisotopes are selected from ⁴⁷Sc, ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ⁹⁰Y, ¹⁰⁹Pd, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁹⁹Au, ²¹¹At, ²¹²Pb, ²¹³Bi, ²²³Ra, ²²⁷Th, ¹⁶¹Tb, ¹⁷⁷Lu, or ²²⁵Ac. 49. The antibody radioisotope construct of claim 47 or 48, wherein the one or more radioisotopes are selected from ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ²¹²Pb, ²¹³Bi, ¹⁶¹Tb, ¹⁷⁷Lu, and combinations thereof. 50. The antibody radioisotope construct of any one of claims 47 to 49, wherein the one or more radioisotopes are ⁸⁹Zr. 51. The antibody radioisotope construct of any one of claims 47 to 50, comprising one chelating linker. 52. The antibody radioisotope construct of any one of claims 47 to 51, comprising more than one chelating linker. 53. The antibody radioisotope construct of any one of claims 47 to 52, wherein the one or more chelating linkers comprise diethylenetriamine pentaacetate (DTPA), deferoxamine (DFO), DFO*, dodecane tetraacetic acid (DOTA), Macropa, and combinations thereof. 54. The antibody radioisotope construct of any one of claims 47 to 53, wherein the one or more linking moieties comprise one or more squaramide moieties, one or more triazole moieties, one or more esters, or a combination thereof. 32591/70242 55. The antibody radioisotope construct of claim 54, wherein the one or more linking moieties comprise one or more squaramide moieties. 56. The antibody radioisotope construct of any one of claims 47 to 55, wherein the chelating linker comprises squaramide-modified diethylenetriamine pentaacetate (DTPA-Sq), squaramide-modified deferoxamine (DFO-Sq), squaramide-modified DFO* (DFO*-Sq), squaramide-modified dodecane tetraacetic acid (DOTA-Sq), or squaramide-modified Macropa (Macropa-Sq). 57. The antibody radioisotope construct of any one of claims 47 to 56, wherein the one or more chelating linkers comprise DFO*-Sq. 58. The antibody radioisotope construct of any one of claims 47 to 57, wherein the antibody moiety: i) has the heavy chain variable region CDR sequences set out in SEQ ID NOs: 6-8 and the light chain variable region sequences set out in SEQ ID NOs: 3-5; or ii) has the chain variable region CDR sequences set out in SEQ ID NOs: 14-16 and the light chain variable region sequences set out in SEQ ID NOs: 11-13. 59. The antibody radioisotope construct of any one of claims 47 to 57, wherein the antibody moiety: i) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 2 and the light chain variable region amino acid sequence set out in SEQ ID NO: 1; or ii) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 10 and the light chain variable region amino acid sequence set out in SEQ ID NO: 9. 60. The antibody radioisotope construct of any one of claims 47 to 57, wherein the antibody moiety comprises MNPR-101. 61. The antibody radioisotope construct of claim 60, wherein the antibody moiety comprises MNPR-101-DFO*-Sq-⁸⁹Zr. 62. The antibody radioisotope construct of claim 60 or 61, wherein the antibody radioisotope construct is MNPR-101-DFO*-Sq-⁸⁹Zr. 63. The antibody radioisotope construct of any one of claims 47 to 62, having a conjugate-to- antibody ratio (CAR) is greater than 1. 64. The antibody radioisotope construct of claim 63, wherein the conjugate-to-antibody ratio (CAR) is between 1 and 5. 32591/70242 65. The antibody radioisotope construct of claim 63 or 64, wherein the conjugate-to-antibody ratio (CAR) is between 1 and 2. 66. The antibody radioisotope construct of any one of claims 63 to 65, wherein the conjugate-to- antibody ratio (CAR) is about 1.5. 67. The antibody radioisotope construct of any one of claims 47 to 62, having a conjugate-to- antibody ratio (CAR) between 0.1 and 1. 68. A drug product comprising the antibody radioisotope construct of any one of claims 47 to 67, one or more antibodies, and a pharmaceutically acceptable excipient. 69. The drug product of claim 68, wherein the antibody radioisotope construct comprises MNPR- 101-DFO*-Sq-⁸⁹Zr, and the one or more antibodies comprise MNPR-101. 70. The drug product of claim 68 or 69, further comprising one or more radioprotectants, a pharmaceutically acceptable carrier, or a combination thereof. 71. The drug product of claim 70, wherein the one or more radioprotectants comprise ascorbic acid, gentisic acid, N-acetyl cysteine, human serum albumin, or a combination thereof. 72. The drug product of any one of claims 68 to 71, wherein the one or more antibodies comprise one or more unconjugated “cold” antibodies. 73. The drug product of claim 72, wherein the one or more unconjugated “cold” antibodies and the antibody of the antibody radioisotope construct are the same. 74. The drug product of claim 72, wherein the one or more unconjugated “cold” antibodies and the antibody of the antibody radioisotope construct are different. 75. The drug product of any one of claims 68 to 74, wherein the total antibody mass dose is about 1 mg to about 80 mg. 76. The drug product of any one of claims 68 to 75, wherein the total antibody mass dose is about 2 mg to about 30 mg. 77. The drug product of any one of claims 68 to 76, wherein the total antibody mass dose is about 4.5 mg to about 20 mg. 78. The drug product of any one of claims 68 to 77, wherein the total antibody mass dose is about 10 mg. 32591/70242 79. The drug product of any one of claims 68 to 78, wherein the conjugate to antibody (CAR) ratio is less than 1. 80. A kit comprising the antibody radioisotope construct of any one of claims 47 to 67 or the drug product of claim 68 to 79, a drug product comprising one or more antibodies, and optionally one or more syringes, one or more filter needles, and/or one or more needles for IV injection. 81. The kit of claim 80, wherein the antibody radioisotope construct comprises MNPR-101-DFO*- Sq-⁸⁹Zr or the drug product comprises a MNPR-101-DFO*-Sq-⁸⁹Zr drug product. 82. The kit of claim 80 or 81, wherein the drug product comprises one or more antibodies comprises a MNPR-101 drug product. 83. The kit of any one of claims 80 to 82, further comprising one or more syringes, one or more filter needles, and/or one or more needles for IV injection. 84. A method of treating a disease or disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the antibody radioisotope construct of any one of claims 47 to 67 or the drug product of any one of claims 68 to 79. 85. A method of treating a disease or disorder in a patient in need thereof, comprising: (i) diagnosing the disease or disorder by administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; (ii) measuring the amount of circulating antibody after administration; (iii) based on the amount of circulating antibody measured after administration, determining if the administered mass dose led to acceptable biodistribution for uPAR-targeted therapy or if it needs to be adjusted, and (iv) adjusting or maintaining the amount of antibody radioisotope construct administered to the patient to achieve a desired clinical effect. 86. The method of claim 84 or 85, wherein the disease or disorder is cancer. 87. A method of treating cancer in a patient in need thereof, comprising: (i) diagnosing cancer in a patient by administering to the patient an antibody radioisotope construct comprising: a radioisotope; a chelating linker; and an antibody moiety specific for human urokinase plasminogen activator receptor (uPAR), wherein the chelating linker comprises one or more squaramide moieties; 32591/70242 (ii) diagnosing the patient with cancer if the ratio of radiation measured in a first tissue compared to a second tissue is 1.5:1 or greater, and (iii) administering to the patient a therapeutically-effective amount of a cancer therapeutic. 88. The method of claim 87, wherein the ratio of radiation measured in the first tissue compared to the second tissue is 2:1 or greater. 89. The method of any one of claims 86 to 88, wherein the cancer is one or more of lung cancer, ovarian cancer, prostate cancer, brain cancer, bladder cancer, head and neck cancer, pancreatic cancer, breast cancer, gastric cancer, or colorectal cancer. 90. The method of any one of claims 85 to 89, wherein the radioisotope is ⁴⁷Sc, ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ⁹⁰Y, ¹⁰⁹Pd, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁹⁹Au, ²¹¹At, ²¹²Pb, ²¹³Bi, ²²³Ra, ²²⁷Th, ¹⁶¹Tb, ¹⁷⁷Lu, or ²²⁵Ac. 91. The method of any one of claims 85 to 90, wherein the radioisotope is ⁸⁹Zr, ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁶⁷Cu, ²¹²Pb, ¹⁶¹Tb, ¹⁷⁷Lu, or ²¹³Bi. 92. The method of any one of claims 85 to 91, wherein the radioisotope is ⁸⁹Zr. 93. The method of any one of claims 85 to 92, wherein the chelating linker comprises one squaramide moiety. 94. The method of any one of claims 85 to 93, wherein the chelating linker comprises squaramide- modified diethylenetriamine pentaacetate (DTPA-Sq), squaramide-modified deferoxamine (DFO-Sq), squaramide-modified DFO* (DFO*-Sq), squaramide-modified dodecane tetraacetic acid (DOTA-Sq), or squaramide-modified Macropa (Macropa-Sq). 95. The method of any one of claims 85 to 94, wherein the chelating linker comprises DFO*-Sq. 96. The method of any one of claims 85 to 95, wherein the antibody moiety comprises an antibody, an antibody fragment, or a non-antibody uPAR-targeting protein. 97. The method of any one of claims 85 to 96, wherein the antibody moiety: i) has the heavy chain variable region CDR sequences set out in SEQ ID NOs: 6-8 and the light chain variable region sequences set out in SEQ ID NOs: 3-5; or ii) has the chain variable region CDR sequences set out in SEQ ID NOs: 14-16 and the light chain variable region sequences set out in SEQ ID NOs: 11-13. 98. The method of any one of claims 85 to 96, wherein the antibody moiety i) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 2 and the light chain variable region amino acid 32591/70242 sequence set out in SEQ ID NO: 1; or ii) has the heavy chain variable region amino acid sequence set out in SEQ ID NO: 10 and the light chain variable region amino acid sequence set out in SEQ ID NO: 9. 99. The method of any one of claims 85 to 96, wherein the antibody moiety comprises MNPR-101 or MNPR-102. 100. The method of claim 99, wherein the antibody moiety comprises MNPR-101. 101. The method of any one of claims 85 to 100, wherein the antibody radioisotope construct is MNPR-101-DFO*-Sq-⁸⁹Zr. 102. The method of any one of claims 87 to 101, wherein the first tissue is tumor tissue. 103. The method of any one of claims 87 to 102, wherein the second tissue is liver tissue, skeletal muscle tissue, or blood. 104. The method of any one of claims 85 to 103, wherein the measuring comprises Positron Emission Tomography (PET). 105. The method of any one of claims 85 to 104, wherein administering the antibody radioisotope construct comprises administering the antibody radioisotope construct to the patient via injection. 106. The method of claim 105, further comprising administering to the patient one or more antibodies. 107. The method of claim 106, wherein the one or more antibodies comprise unconjugated “cold” antibodies. 108. The method of claim 106 or 107, wherein the one or more antibodies comprise MNPR-101.