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WO2012000861A1 - Aptamère marqué au carbone 11 (11c) permettant de détecter un tissu malade - Google Patents

Aptamère marqué au carbone 11 (11c) permettant de détecter un tissu malade Download PDF

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Publication number
WO2012000861A1
WO2012000861A1 PCT/EP2011/060421 EP2011060421W WO2012000861A1 WO 2012000861 A1 WO2012000861 A1 WO 2012000861A1 EP 2011060421 W EP2011060421 W EP 2011060421W WO 2012000861 A1 WO2012000861 A1 WO 2012000861A1
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WO
WIPO (PCT)
Prior art keywords
aptamer
amino acid
carbon atom
diseased tissue
tissue
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2011/060421
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German (de)
English (en)
Inventor
Hartmuth C. Kolb
Ursus KRÜGER
Oliver Lade
Arno Steckenborn
Tanja Weil
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Siemens AG
Max Planck Gesellschaft zur Foerderung der Wissenschaften
Siemens Corp
Original Assignee
Siemens AG
Max Planck Gesellschaft zur Foerderung der Wissenschaften
Siemens Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Siemens AG, Max Planck Gesellschaft zur Foerderung der Wissenschaften, Siemens Corp filed Critical Siemens AG
Publication of WO2012000861A1 publication Critical patent/WO2012000861A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57434—Specifically defined cancers of prostate
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/16—Aptamers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3517—Marker; Tag
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/10—Applications; Uses in screening processes

Definitions

  • the invention relates to the use of an aptamer for Her ⁇ position of an agent for detecting a diseased tissue. It further relates to a radiopharmaceutical for the localization of a diseased tissue comprising such an aptamer.
  • biochemical analyzes of blood, other body fluids and tissue samples are used to characterize diseases. It examines the presence and amount of molecules that are typical of a particular disease. In addition to foreign substances also endogenous substances are detected, which are ⁇ example, only formed in an infection by viruses or bacteria.
  • tumor cells frequently form large amounts of certain proteins, in particular cellular receptors whose expression is specific for a type of tumor.
  • proteins that are made specifically from diseased cells are surface molecules that are anchored in the membrane which he ⁇ diseased cells. These surface molecules can be detected by appropriate diagnostic procedures. For this purpose, usually cells from tissue or blood samples are examined with antibodies that bind to specific, specific for a disease surface molecules. Such in vitro studies can diagnose the presence of a disease.
  • ectopic cell aggregates such as tumors or swellings of individual organs, can be used with them. locate gane.
  • a diseased tissue shows no marked morphological abnormalities, or is relatively small, it can easily be overlooked in traditional studies.
  • the invention is therefore based on the object, an agent be ⁇ riding determine by which a diseased tissue can be specifically and regardless of its size detected.
  • This object is achieved by the use of an aptamer for the manufacture of an agent for detecting a lung diseased tissue ge ⁇ dissolves.
  • aptamer refers to short, single-stranded nucleic lein Textre oligomers that can accommodate both RNA and DNA molecules to ⁇ . Depending on their respective sequence aptamers form diverse structures and bind to Zielmo ⁇ leküle of various classes. This results in a specific structural compatibility between an aptamer and its target molecule, similar to antigen-antibody binding.
  • the structure compatibility of the molecules occurs via electrostatic interactions, ionic Bin ⁇ compounds, van der Waals interactions, hydrogen bonds and so-called. Stacking interactions between the aromatic rings of the bases of nucleic acids.
  • Aptamers that bind to a specific target molecule are identified and produced through in vitro selection and amplification techniques known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment) processes.
  • Aptamers comprise regularly 8-220 nucleic ⁇ otide, preferably 20 to 60 nucleotides. However, it is also possible to use aptamers with up to 500 nucleotides. she can be synthesized or obtained by enzymatic degradation of genomic DNA (Kulbachinskiy AV, 2007).
  • aptamers can be identified that bind a specific Zielmole ⁇ kül. This can be both larger biomolecules, such as proteins, as well as to individual chemical ele ⁇ ments. In addition, aptamers bind almost all classes of substances, so that aptamers can also be identified that recognize and bind to specific protein modifications, such as fatty acid or sugar modifications.
  • Each cell carries on its surface, anchored in its cell membrane, a multitude of different molecules, most of which belong to the class of proteins. Besides Mole ⁇ cules with basic biological functions that are found in almost every cell, many molecules only by cells of a particular tissue or a particular cell type can be expressed. In addition, cells that are infested with pathogens or have impaired cell functions, such as tumor cells, form their own molecules. Many of these disease-specific molecules are membrane bound and Queen ⁇ NEN be detected on the surface of the respective cell.
  • an aptamer is selected that interacts with one, indicative of an abnormal tissue molecule, am ⁇ det the aptamer specifically to the pathological tissue.
  • the aptamer is selected so that the bond between the aptamer and the target molecule is a linear coefficient called. KD value of ⁇ 100 nM, preferably ⁇ 10 nM, which most preferably of 7.5 nM. With such a
  • Aptamer can be specifically detected even a few cells of a diseased tissue.
  • diseased tissue refers to cells, parts of organs or whole organs that do not or not fully fulfill their physiological function. These include, for example, viruses or bacteria infected cells hy pertrophes tissue, inflamed tissue and organs, hyperplasti ⁇ MOORISH and neoplastic tissue, such as ulcers, tumors and cancers.
  • Diseased cells often form proteins whose expression is indicative of a particular disease, for example, because they are derived from the genetic material of a virus or bacterium. When these molecules are cell surface molecules, they are anchored to the cell membrane. By specifically binding a surface molecule of a diseased tissue, the aptamer enables a reliable localization of this tissue.
  • the aptamer is coupled to an amino acid, which in turn has an 11 C carbon atom.
  • positrons also referred to as ß + radiation, are formed. Push the positrons on
  • Electron they form two photons, which at an angle of 180 °, so exactly in the opposite direction, from each other.
  • the photons can be detected and from this the position of the positron emission, or of the 11 C carbon atom, can be calculated.
  • the Men are ⁇ ge of aptamers, which is located at a certain point, quantified.
  • the coupling of an amino acid with an 11 C carbon atom to the aptamer used in the invention makes it possible to detect and image both the presence and the position of the aptamer.
  • the processes described in patent applications DE 10 2009 035 648.7 and DE 10 2009 035 645.2 are particularly suitable.
  • the labeling the aptamer with a C-carbon atom via an amino acid is particularly advantageous because there ⁇ by any of the usual chelating agents such as diethylenetriamine aminpentaacetat (DTPA), 1, 4, 7, 10-tetraazacyclododecane-
  • DTPA diethylenetriamine aminpentaacetat
  • 1, 4, 7, 10-tetraacetic acid must be used.
  • the resulting complex of aptamer and amino acid comprises kör ⁇ pereigene molecules, whereby it is particularly compatible for the organism.
  • Both the aptamer and its single nucleic acids, as well as the amino acid are non-toxic. They can of course be metabolized, broken down and excreted.
  • By using an integrated X1 C carbon atom it is also possible to prevent a ra- 1
  • diooxider impurity such as fluorine, xenon, or 68 gallium, must be introduced into the organism.
  • a further advantage of the labeled via an amino acid with 1X C- carbon aptamer is in the low-Sig nal ⁇ / background ratio during detection of the aptamer.
  • the aptamer binds to the diseased tissue, whereas free, unbound aptamers are rapidly metabolised and excreted from the organism because they are rapidly degraded by endogenous enzymes. This creates a strong and specific signal at the location of the diseased tissue, and the background signal is minimized.
  • the agent is a radiopharmaceutical.
  • radiopharmaceuticals refers to medicines containing radionuclides whose radiation is used for diagnosis and therapy.
  • the main applications are in oncology, Kar ⁇ ogy and neurology, as well as pharmaceutical research.
  • radionuclides gamma or beta-emitting nuclides, for example 133 xenon, "technetium, 68 gallium, and fluorine, used. They are usually about Kom ⁇ formers such as DTPA, DOTA or ethylenediaminetetraacetate (EDTA) bound to mono- or polysaccharides.
  • the nuclides are detected by scintigraphy, single photon emission computed tomography (SPECT) or positron emission tomography (PET), depending on the nature of their radiation.
  • SPECT single photon emission computed tomography
  • PET positron emission tomography
  • conventional diet drugs can cause side effects, such as anaphylactic or allergic reactions, in the body of a patient.
  • the use of an aptamer from the body's own nucleic acids significantly reduces this risk because neither the aptamer itself nor its degradation products are toxic.
  • carbon is an element found in the body that naturally can be metabolized.
  • the amino acid is glycine, alanine, valine or serine.
  • the use of one of these amino acids to couple the 11 C-carbon isotope to the aptamer is particularly advantageous because these amino acids are relatively small and have no reactive side chains. Therefore, they neither affect the conformation nor the binding affinity of the aptamer, and the specificity of the aptamer for its target molecule is retained.
  • the amino acid is coupled via a peptide bond to a free amino group of a nucleotide of the aptamer.
  • the Apt ⁇ mer forth ⁇ tional methods of peptide synthesis such as solid phase synthesis, the coupling of the amino acid.
  • the preparation of the complex is therefore possible without expensive additional synthesis process, where ⁇ is reduced by the technical and financial effort.
  • the complex of aptamer and amino acid can be can be used directly after attaching the 11 C-labeled amino acid. 11C carbon has a half-life of only about 20 minutes, so the longer the time between synthesis of the complex and its use, the higher the radiation dose must be.
  • the aptamer can then be used immediately ⁇ the. In this way, the time between the proces ⁇ processing of the C-11 carbon and the use of the aptamer is re- pokerd so that the radiation loss is minimized during the herstel ⁇ development of the complex. Therefore, the radiation dose ⁇ which must be ⁇ sets in the processing of the 11 C-carbon can to ensure a certain strength of the radiation Pro ⁇ domestic product may be correspondingly lower. The manufacturer's position is more cost-effective and thereby the radiation exposure for the technical staff that provides the agent ago ⁇ reduced.
  • the 11 C carbon atom is the carbonyl carbon atom of the peptide bond.
  • the peptide bond is relatively protected inside the complex of aptamer and amino acid. This ensures that the 11 C carbon atom is not split off from the amino acid, as would be possible with an exposed side chain of the amino acids.
  • the amino acid is a D-amino acid.
  • D-amino acid With the exception of glycine besit ⁇ zen all amino acids at its C-alpha-carbon atom is a chiral center and may therefore as configurational isomers, namely as D- or L-amino acid present.
  • Endogenous peptides and proteins are largely composed of amino acids in L configuration.
  • most natural proteases and peptidases work stereoselectively and metabolise mainly L-amino acids. Therefore, the degradation of D-amino acids by endogenous enzymes takes longer than that of L-amino acids.
  • This fact can be used to prolong the half-life of the complex between aptamer and an amino acid by a D-amino acid ⁇ is used instead of an L-amino acid (Neundorf I et al., 2008).
  • a D-amino acid ⁇ is used instead of an L-amino acid
  • Another way to delay the cleavage is to use a non-natural amino acid.
  • the non-natural amino acids are metabolized more slowly because the body's own proteolytic enzymes are specially adapted to the breakdown of natural amino acids.
  • other chemical modifications of the amino acid are possible.
  • the terminal amino group of the amino acid can be replaced by an isonitrile group. Such a modification reduces the amino group mediated interaction with proteolytic enzymes without altering the binding specificity.
  • Another object of the invention is a radiopharmaceutical for the localization of a tumor comprising an aptamer.
  • the aptamer binds to the tumor and is gekop ⁇ pelt to an amino acid, which in turn comprises a C-11 carbon atom gron- NEN even a few cells of the tumor are located.
  • the radiopharmaceutical of the present invention provides a sensitive and specific agent for determining the position of a tumor in vivo.
  • the radiopharmaceutical is administered to the patient and the aptamers contained therein, which are coupled to the 11 C-labeled amino acids, are distributed quickly and efficiently in the body due to their size. They bind to the tumor and collect on its surface.
  • the accumulation of radioactively labeled aptamers is detected by positron emission tomography (PET) to determine the exact location of the tumor in the patient's body.
  • PET positron emission tomography
  • the amino acid is glycine, alanine, valine or serine, so that neither the conformation nor the binding affinity of the aptamer is influenced by the amino acid.
  • the C-carbon atom is the carbon atom of the terminal ⁇ -carboxyl group of the amino acid.
  • the X1 C carbon atom can not be split off from the amino acid, as would be possible with an exposed side chain of the amino acids.
  • the radiopharmaceutical is a PET biomarker.
  • PET is an established method for detecting the radiation of radioactive elements and determining their position (Massoud TF, Gambhir SS, 2003). With the aid of detector devices arranged annularly around the patient, sectional images are created on which the decay events in their spatial distribution in the interior of the body are represented. The PET also makes it possible to determine the amount of mar ⁇ -labeled molecules quantitatively in a tissue.
  • a method for localization of a diseased tissue comprising the steps of: a) providing an aptamer, which is coupled to an amino acid ⁇ ; b) administering the aptamer to the Or ⁇ organism; and c) detecting the aptamer in the organism by positron emission tomography (PET).
  • PET positron emission tomography
  • aptamer according to the invention to which a 11 C-labeled amino acid is coupled to a morbid Ge ⁇ tissue is detected in the interior of an organism and localized, and can thus be in the body of a patient observed. In this way, for example, the size or extent of an infection or a tumor can be determined.
  • the aptamer According to the invention used is therefore ideal for Be ⁇ observation of progress and success of a treatment, so-called. Therapy monitoring, appropriate.
  • FIG. 1 shows schematically an aptamer 1 with 14 nucleotides 3, which is bound to a pathological tissue 18.
  • the aptamer 1 is coupled to an amino acid 2 which is linked to an X1 C-
  • Carbon atom is radiolabeled.
  • the radioactive label is represented by an asterisk (*).
  • the specific binding affinity between the aptamer 1 and the pathological tissue 18 comes off due to chemical exchange ⁇ effects between the aptamer 1 and the surface of the diseased tissue 18th
  • the pathological tissue 18 forms surface molecules that are characteristic of the disease of the tissue ⁇ esp.
  • an aptamer 1 is identified that interacts with a surface molecule of diseased tissue 18.
  • an amino acid labeled with a C-carbon atom is coupled to the aptamer 1.
  • the aptamer 1 can then be replaced by the positrons emitted upon the decay of the ⁇ C carbon atom be detected by positron emission tomography (PET).
  • PET positron emission tomography
  • the aptamer 1 coupled to an 11 C-labeled amino acid 2 is administered to a patient in the form of a drug. It binds to the pathological tissue 18 and collects on its cells. This accumulation becomes visible in a PET, so that the distribution of the aptamer 1 or the position of the diseased tissue 18 in the body of the patient can be determined.
  • FIG. 2 shows a representation of an aptamer by means of a chemical formula.
  • the aptamer has the sequence SEQ ID No .: 1 and is gekop ⁇ pelt to a 11 C-labeled amino acid, namely, glycine.
  • the aptamer comprises 70 nucleic acids of the following sequence: GGG AGG ACG AUG CGG ACC GAA AAA GAC CUG ACU UCU AUA CUA AGU CUA CGU UCC CAG ACG ACU CGC CCG A.
  • the 3 'terminal adenosine of the aptamer and it gekop ⁇ pelte glycine are represented by structural formula, and the remaining nucleic acids 3 by their respective letter code.
  • the sequence of the aptamer is also given in SEQ ID NO: 1.
  • the carbonyl carbon glycine is an X1 C carbon atom represented by the number 11 above the carbonyl carbon atom.
  • the aptamer of SEQ ID NO .: 1 has a specific binding affinity Bin ⁇ specific to the prostate membrane antigen (PSMA) on.
  • PSMA prostate membrane antigen
  • This protein is mainly expressed in prostate tissue and comes in prostate carcinomas in particularly high Quantities.
  • PSMA is a membrane protein present in healthy prostate cells but in a particular cytoplasmic form. In prostate cancer, it is mainly located on the cell membrane of tumor cells.
  • the aptamer 1 is selected and amplified by its binding specificity to PSMA with SELEX methods from an aptamer library. Subsequently, the 11 C-labeled amino acid ⁇ 2 is coupled to a conventional peptide synthesis methods to the aptamer. 1 The aptamer 1 is administered to the patient and thus the prostate carcinoma by PET Darge ⁇ presents. In this way, metastases which also express membrane-bound PSMA can be localized.
  • Figure 3 shows a schematic representation (greatly simplified by Faller A, Schünke M, The human body, Thieme, 2008) of a circulatory system 10 of an organism and the distribution of an aptamer 1 therein.
  • the circulation system 10 includes various organs schematically represented, such as the lungs 12, heart 13, liver 14, 15 intestine and kidney 16 and the main wires 11 which these organs ver ⁇ bind.
  • the aptamer 1 is represented by triangles along the wires 11.
  • the degradation products 17 of the aptamer 1 are represented by individual lines within the outline of the kidney 16 Darge ⁇ .
  • Left of center of the circulatory system 10 is additionally ⁇ a diseased tissue 18, for example, a tumor or an inflammation, shown, are attached to the increased aptamers. 1
  • Phase I The aptamer 1 is injected into the circulatory system 10 of the organism.
  • Phase II is via the blood circulation system 10, the aptamer 1 in the organs 12, 13, 14, 15, and 16 of the ⁇ organism transported advantage.
  • Phase III The circulating aptamer 1 binds specifically to the diseased tissue 18.
  • Phase IV Unbound aptamer 1 is rapidly metabolised and enzymatically degraded.
  • the organism not failed ⁇ det between the body's own molecules and the aptamer 1, because it is constructed from nucleic acids 3 and an amino acid 2, which correspond to the body's own molecules.
  • the degradation products 17 of the aptamer 1 and the nucleic acids 3 and the amino acid 2 accumulate predominantly in the kidney 16, from where they are excreted via the bladder and the ureter.
  • Massoud TF, Ga bhir SS Molecular imaging in living subjects: seeing fundamental biological processes in a new light; Genes Dev. 2003 Mar 1; 17 (5): 545-80.

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Abstract

La présente invention concerne l'utilisation d'un aptamère (1) pour produire un agent permettant de détecter un tissu malade (18). Ledit aptamère (1) se lie au tissu malade (18) et est couplé à un acide aminé (2) qui présente un atome de carbone 11 (11C). L'invention concerne également un produit radiopharmaceutique permettant de localiser une tumeur (18) et comprenant un tel aptamère (1).
PCT/EP2011/060421 2010-06-30 2011-06-22 Aptamère marqué au carbone 11 (11c) permettant de détecter un tissu malade Ceased WO2012000861A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE201010026066 DE102010026066A1 (de) 2010-06-30 2010-06-30 11C-markiertes Aptamer zur Detektion eines krankhaften Gewebes
DE102010026066.5 2010-06-30

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WO2012000861A1 true WO2012000861A1 (fr) 2012-01-05

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2711645C1 (ru) * 2019-06-26 2020-01-17 Федеральное государственное бюджетное учреждение "Федеральный Сибирский научно-клинический центр Федерального медико-биологического агентства" (ФГБУ ФСНКЦ ФМБА России) Способ получения активной фармацевтической субстанции для синтеза радиофармпрепарата, тропного к клеткам карциномы Эрлиха

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070041901A1 (en) * 2002-06-18 2007-02-22 Diener John L Stabilized aptamers to PSMA and their use as prostate cancer therapeutics
DE102009035645A1 (de) 2009-07-29 2011-02-03 Siemens Aktiengesellschaft Verfahren zur Herstellung eines radioaktiv markiertren Peptids
DE102009035648B3 (de) 2009-07-29 2011-03-17 Siemens Aktiengesellschaft Verfahren zur Herstellung eines radioaktiv markierten Carboxylats sowie die Verwendung einer Mikroelektrode zur elektrochemischen Synthese eines radioaktiv markierten Carboxylats

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100183504A1 (en) * 2007-06-14 2010-07-22 Fanqing Frank Chen Multimodal imaging probes for in vivo targeted and non-targeted imaging and therapeutics

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070041901A1 (en) * 2002-06-18 2007-02-22 Diener John L Stabilized aptamers to PSMA and their use as prostate cancer therapeutics
DE102009035645A1 (de) 2009-07-29 2011-02-03 Siemens Aktiengesellschaft Verfahren zur Herstellung eines radioaktiv markiertren Peptids
DE102009035648B3 (de) 2009-07-29 2011-03-17 Siemens Aktiengesellschaft Verfahren zur Herstellung eines radioaktiv markierten Carboxylats sowie die Verwendung einer Mikroelektrode zur elektrochemischen Synthese eines radioaktiv markierten Carboxylats

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
FALLER A, SCHÜNKE M: "Der Körper des Menschen", 2008, THIEME-VERLAG
JAVIER DJ, NITIN N, LEVY M, ELLINGTON A, RICHARDS-KORTUM R: "Aptamer-targeted gold nanoparticles as molecular-specific contrast agents for reflectance imaging", BIOCONJUG CHEM., vol. 19, no. 6, June 2008 (2008-06-01), pages 1309 - 12
JOHNSTRÖM P ET AL: "11C-labelled glycine: synthesis and preliminary report on its use in the investigation of intracranial tumours using positron emission tomography.", INTERNATIONAL JOURNAL OF RADIATION APPLICATIONS AND INSTRUMENTATION. PART A, APPLIED RADIATION AND ISOTOPES 1987 LNKD- PUBMED:2822628, vol. 38, no. 9, 1987, pages 729 - 734, XP009014077, ISSN: 0883-2889 *
KOBORI N ET AL: "VISUALIZATION OF MRNA EXPRESSION IN CNS USING 11C-LABELED PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE", NEUROREPORT, LIPPINCOTT WILLIAMS & WILKINS, US, vol. 10, no. 14, 29 September 1999 (1999-09-29), pages 2971 - 2974, XP009014077, ISSN: 0959-4965, DOI: 10.1097/00001756-199909290-00018 *
KULBACHINSKIY AV: "Methods for selection of aptamers to protein targets", BIOCHEMISTRY (MOSC);, vol. 72, no. 13, December 2007 (2007-12-01), pages 1505 - 18, XP002593035, DOI: doi:10.1134/S000629790713007X
MASSOUD TF, GAMBHIR SS: "Molecular imaging in living subjects: seeing fundamental biological processes in a new light", GENES DEV., vol. 17, no. 5, 1 March 2003 (2003-03-01), pages 545 - 80, XP007905304, DOI: doi:10.1101/gad.1047403
NEUNDORF I, RENNERT R, FRANKE J, KÖZLE I, BERGMANN R: "Detailed analysis concerning the biodistribution and metabolism of human calcitonin-derived cell-penetrating peptides", BIOCONJUG CHEM., vol. 19, no. 8, August 2008 (2008-08-01), pages 1596 - 603, XP002575961, DOI: doi:10.1021/bc800149f
YOUNES C K ET AL: "Labelled oligonucleotides as radiopharmaceuticals: Pitfalls, problems and perspectives", CURRENT PHARMACEUTICAL DESIGN, BENTHAM SCIENCE PUBLISHERS, NL, vol. 8, no. 16, 1 July 2002 (2002-07-01), pages 1451 - 1466, XP009154303, ISSN: 1381-6128 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2711645C1 (ru) * 2019-06-26 2020-01-17 Федеральное государственное бюджетное учреждение "Федеральный Сибирский научно-клинический центр Федерального медико-биологического агентства" (ФГБУ ФСНКЦ ФМБА России) Способ получения активной фармацевтической субстанции для синтеза радиофармпрепарата, тропного к клеткам карциномы Эрлиха

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