WO2012000866A1 - Peptide marqué 11c pour la détection d'un tissu malade - Google Patents

Peptide marqué 11c pour la détection d'un tissu malade Download PDF

Info

Publication number
WO2012000866A1
WO2012000866A1 PCT/EP2011/060448 EP2011060448W WO2012000866A1 WO 2012000866 A1 WO2012000866 A1 WO 2012000866A1 EP 2011060448 W EP2011060448 W EP 2011060448W WO 2012000866 A1 WO2012000866 A1 WO 2012000866A1
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
hla
antigen
amino acid
antigen complex
Prior art date
Application number
PCT/EP2011/060448
Other languages
German (de)
English (en)
Inventor
Oliver Lade
Jan Alexander Hiss
Hartmuth C. Kolb
Ursus KRÜGER
Gisbert Schneider
Arno Steckenborn
Original Assignee
Siemens Aktiengesellschaft
Johann Wolfgang Goethe-Universität
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 Aktiengesellschaft, Johann Wolfgang Goethe-Universität filed Critical Siemens Aktiengesellschaft
Publication of WO2012000866A1 publication Critical patent/WO2012000866A1/fr

Links

Classifications

    • 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
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/60—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances involving radioactive labelled substances
    • 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
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70539—MHC-molecules, e.g. HLA-molecules

Definitions

  • the invention relates to the use of a peptide for the manufacture ⁇ position of an agent for detecting a diseased tissue. It further relates to a radiopharmaceutical for the localization of a diseased tissue comprising such a peptide. In modern diagnostics are used to characterize
  • 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.
  • Object is achieved by the use of a peptide for the manufacture ⁇ development of an agent for detecting a pathological tissue, which forms a human leukocyte antigen (HLA) antigen complex.
  • HLA human leukocyte antigen
  • TCR TCR Receptor
  • peptide refers to an organic compound of at least two amino acids linked via a peptide bond. It includes both oligopeptides of up to about ten amino acids, as well as polypeptides of up to about 30 amino acids, regardless of their primary, secondary or tertiary structure. Both naturally occurring and biotechnologically or synthetically produced compounds are included.
  • the peptide used in the present invention is selected to have an amino acid sequence of a CDR3 loop of a TCR directed against an HLA antigen complex of the diseased tissue. Almost all cells of the human body present peptides, which are fragments of proteins that are inside them, on their surface. Specialized cells of the immune system recognize the protein fragments and distinguish whether they are of the body's own and foreign origin.
  • HLA antigen complex refers to a complex of an HLA transmembrane protein which is also “major histocompatible”. bility complex "(MHC) is called, and an antigen.
  • antigen denotes short-chain peptides or protein fragments, resulting in the degradation of their own and others pro ⁇ teinen in the cell and anchored by an HLA on the cell surface
  • the extracellular part of the HLA-antigen complex is recognized and bound by T-cells of the immune system, based on the interactions between the antigen of the HLA-antigen complex and the T-cell TCR
  • Two identical or different polypeptide chains (A, B) that bind together to form the HLA-antigen complex have been found so far: In total, four different human TCR polypeptide chains have been identified, designated alpha, beta, gamma and delta a highly variable region, the so-called complementarity determining region (CDR) 3 loop.) The amino acid sequence of the CDR3 loop is different in the TCR of each T cell and esp Takes the binding specificity of the receptor.
  • CDR complementarity determining region
  • the TCR binds only a specific protein fragment (antigen) because the amino acids of the CDR3 loop interact specifically with the amino acids of the antigen.
  • the CDR3 loop may be about two to 21 amino acids in length. It usually comprises about 7 to 14 amino acids (Rock et al., 1994).
  • the amino acid sequence of the peptide used in the present invention binds the same antigen as the TCR.
  • To determine the Ami ⁇ acid sequence of a CDR3 loop are isolated T cells from the blood of a patient and grown clonally in culture. Since a T cell expresses only an individual TCR, the cells of a T cell clone all produce the same TCR. From the cells of a clone the DNA Se acid sequence of the TCR or the CDR3 loop is Polymerasenketten- reactions with specific primers amplified and sequenced. Subsequently, a peptide with this sequence is Herge ⁇ provides that has the same binding specificities as the TCR.
  • the peptide is chosen so that the bond between the peptide and the HLA antigen complex is a linear coefficient called. KD value of ⁇ 100 nM, be ⁇ vorzugt of ⁇ 10 nM, most preferably of 7, 5 nM on ⁇ points.
  • KD value of ⁇ 100 nM be ⁇ vorzugt of ⁇ 10 nM, most preferably of 7, 5 nM on ⁇ points.
  • 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 typical of a particular disease, for example because they are derived from the genetic material of a virus or bacterium. The cell then presents HLA complexes on their surface bind the fragments of these pro ⁇ proteins so that they can be recognized by a TCR. By specifically binding the antigen of the HLA-antigen complex, the peptide allows a reliable localization of the diseased tissue.
  • positrons also referred to as ß + radiation
  • ß + radiation Upon decay of the X1 C carbon isotope, positrons, also referred to as ß + radiation, are formed. If the positrons hit an electron, they form two photons, which move away from each other at an angle of 180 °, ie exactly in the opposite direction. The photons can be detected and from this the position of the positron emission, or the 11 C- Carbon atoms, to be calculated.
  • the integration of a C-11 carbon atom in the peptide used according to the invention allows both the presence of as well as the positi on of the peptide ⁇ detect and image.
  • An advantage of using an 11 C-labeled peptide is its structure of endogenous amino acids, making it compatible with the organism.
  • the peptide and its individual amino acids are non-toxic, they can of course be metabolized, broken down and excreted.
  • the use of an integrated 11 C carbon atom also makes it possible to prevent a radioactive foreign substance, such as fluorine, xenon, or gallium, from having to be introduced into the organism.
  • Another advantage of the peptide directly labeled with X1 C lies in the favorable signal / background ratio during the detection of the peptide.
  • the peptide binds to the HLA complex, with which it forms a stable compound that is difficult to access for enzymatic degradation. Free, unbound peptides, however rapidly metabolized and excreted from the Or ⁇ organism because they are degraded rapidly by endogenous enzymes. This results in a strong and specific signal at the position of the HLA-antigen complex, and the background signal is minimized.
  • the agent is a radiopharmaceutical.
  • radiopharmaceuticals records 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 are gamma or beta radiation emitting nuclides, for example Xenon 133, "technetium, gallium 68, fluorine 18 and used.
  • Kom ⁇ formers such as diethylene triamine pentaacetate (DTPA), 1,4,7,10 - tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) or ethylenediaminetetraacetate (EDTA) bound to mono- or polysaccharides
  • DTPA diethylene triamine pentaacetate
  • DOTA 1,4,7,10 - tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid
  • EDTA ethylenediaminetetraacetate
  • the nuclides are, depending on the nature of their radiation, by scintigraphy, Single Photon Emission Computed Tomography (SPECT) or positron emission tomography (PET) is detected. Because of their non-physiological constituents parts but conventional radiopharmaceuticals can Crowddlingun ⁇ gen as anaphylactic or allergic reactions that cause the Kör ⁇ by a patient.
  • the C-carbon atom is a carbonyl carbon atom of an amino acid.
  • the carbonyl groups are part of the peptide bonds between the amino acids and are located inside the peptide. This ensures that the ⁇ C carbon atom is not cleaved off the peptide, as would be possible with a side chain of one of the amino acids.
  • the C-carbon atom is the carbonyl carbon atom of the N-terminal amino acid of the peptide.
  • This embodiment is particularly preferred because the peptide can be used directly after the on ⁇ bring the 11 C-labeled amino acid.
  • 11 C-carbon has a half-life of only about 20 Minu ⁇ th, so that the radiation dose must be chosen the higher, the more time is between the synthesis of the peptide and its ⁇ ner use. If the 11 C-labeling with the N-terminal amino acid and thus in the last step of the synthesis is applied, the peptide can be used immediately after its synthesis.
  • the time between the processing of the 11 C carbon and the use of the peptide is reduced, so that the radiation loss during the preparation of the peptide is minimized. Therefore, the radiation dose that must be used in the processing of the 11 C carbon to ensure a certain radiation intensity of the product, be correspondingly lower.
  • the peptide has at least one D-amino acid.
  • D-amino acid With the exception of glycine, all amino acids have a chiral center at their alpha carbon atom and can therefore exist as configurational isomers, namely as the D or L amino acid.
  • Endogenous peptides and proteins are largely composed of amino acids in L configuration.
  • most natural proteases and peptidases work stereoselectively and metabolize mainly L-amino acids. Therefore, the degradation of D-amino acids by endogenous enzymes takes longer than that of L-amino acids.
  • non-natural amino acids are metabolized more slowly because the body's own proteolytic enzymes are specially adapted to the degradation of natural amino acids.
  • the unnatural amino acids should be chosen, however, that the binding affinity of the peptide is not changed ⁇ changed.
  • other chemical modifications of individual amino acids of the peptide are possible in order to obtain the
  • Example ⁇ as can be Replace the terminal amino group of the peptide by a isonitrile. Such modification redu ⁇ the sheet, conveyed from the amino group, interaction with proteolytic enzymes without altering the bond between the peptide used in the invention and the antibody.
  • Another object of the invention is a radiopharmaceutical comprising a peptide having an 11 C carbon atom for the localization of a diseased tissue which forms an HLA antigen complex.
  • the peptide has an amino acid sequence of a complementary determining region (CDR) 3 loop of a TCR directed against the HLA-antigen complex. As a result, the peptide binds specifically to the antigen of the HLA
  • the radiopharmaceutical according to the invention provides a sensitive and specific agent for determining the position of a diseased tissue in vivo.
  • the radiopharmaceutical is administered to the patient, and the peptides contained therein are rapidly and efficiently distributed in the body because of their size. They bind to the HLA antigen complex of diseased tissue and collect on its surface. This tissue can play as a center of inflammation to be infected cells or tumor by viruses or bacteria at ⁇ .
  • the accumulation of radioactively labeled peptides is detected by positron emission tomography (PET), which determines the exact position of the infected cells, the inflammation or the tumor in the patient's body.
  • PET positron emission tomography
  • the 11 C-carbon atom is a carbonyl carbon atom of an amino acid, preferably the carbonyl carbon atom of the N-terminal amino acid of the peptide.
  • 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 are represented in their spatial distribution in the interior of the body. The PET also makes it possible to determine the amount of mar ⁇ -labeled molecules quantitatively in a tissue.
  • a method of localizing a diseased tissue in an organism comprising the steps of a) providing a peptide, b) administering the peptide to the organism, c) detecting the peptide in the organism Organism using positron emission tomography (PET).
  • PET positron emission tomography
  • the peptide has an amino acid sequence of a CDR3 loop of a T cell receptor (TCR), which is directed against the HLA antigen complex, and binds to an antigen of the HLA antigen complex.
  • TCR T cell receptor
  • the peptide also has an 11 C carbon atom.
  • an antigen of an HLA-antigen complex is tektiert de- inside an organism, and isolated, so that the distribution of an HLA antigen complex, observed in a patient's body ⁇ the can. In this way, for example, the size or extent of an infection or a tumor can be determined.
  • the peptide used according to the invention is therefore outstandingly suitable for observing the course and success of a treatment, so-called therapy monitoring.
  • FIG. 1A schematically shows a diseased tissue 18 on the surface of which a human leukocyte antigen (HLA) 5 with an antigen 4 is located. Together they form an HLA-antigen complex 20, to which in turn a T-cell receptor (TCR) 6 is attached.
  • the TCR 6 consists of two different polypeptide chains (A, B) (8, 9), both of which have a highly variable region, a so-called CDR3 loop 7.
  • the CDR3 loop 7 binds directly to the antigen 4.
  • the HLA 5 is formed by the cells of the diseased tissue 18 and presented on its surface. HLA 5 binds short peptides from proteins inside the cell descend and act as antigens 4.
  • the TCR 6 recognizes the antigen 4 and binds the HLA-antigen complex 20.
  • the specifi ⁇ specific binding affinity between the HLA-antigen complex 20 and the TCR 6 comes about due to chemical interactions between the antigen 4 and the CDR3 loop 7 , Its amino acid sequence determines the specificity of TCR 6, which recognizes and binds only one particular antigen 4.
  • FIG. 1B schematically shows peptide 1 bound to antigen 4.
  • Peptide 1 comprises nine amino acids 2, of which the N-terminal amino acid 3 is radioactively labeled with an 11 C carbon atom. The radioactive label is represented by an asterisk (*).
  • the amino acid sequence of the 11 C-labeled peptide 1 corresponds to the amino acid sequence of the CDR3 loop 7 of the TCR 6, such that the peptide 1, the binding affinity of the CDR3 loop be sitting ⁇ 7 and specifically binds to the antigen.
  • 4 Due to the binding specificity ser ⁇ the 11 C-labeled peptide 1 for de- tetechnisch 4 of the antigen may be used.
  • the positrons released upon decay of the 11 C carbon are detected by positron emission tomography (PET). The location of the positron emission corresponds to the location of the peptide 1 and the antigen 4 bound thereto.
  • PET positron emission tomography
  • the DNA region of the CDR3 loop 7 of a TCR 6 is selectively amplified and sequenced. Subsequently, an 11 C-labeled peptide 1, corresponding to the amino acid sequence of the CDR3 loop 7, is produced.
  • Peptide 1 is administered to the patient in the form of a pharmaceutical composition binds to the antigen 4 and accumulates in the cells of the krankhaf ⁇ th tissue 18, such as a tumor. This accumulation is seen in positron emission tomography (PET). bar, so that the distribution of the antigen 4 or the position of the tumor 18 in the body of the patient can be determined. In this way, newly formed metastases carrying the HLA-antigen complex 20 are detected by means of PET.
  • PET positron emission tomography
  • FIG. 2 shows a representation of a peptide having the sequence SEQ ID NO: 1 by means of a chemical formula.
  • the peptide comprises 9 amino acids 2 of the following sequence: arginine-serine-glycine-tyrosine-asparagine-threonine-aspartate-lysine-leucine-isoleucine.
  • the N-terminal arginine is by structural formula represents ⁇ Darge, the following amino acids 2 by their respective three-letter code.
  • the sequence of the peptide is also given in SEQ ID NO: 1.
  • the carbonyl carbon atom of N-terminal arginine is an 11 C carbon atom, represented by the number 11 above the carbonyl carbon atom.
  • Peptide 1 is prepared by conventional protein synthesis methods and the 11 C-labeled N-terminal amino acid 3 is added in the last step, because the half-life of the X1 carbon carbon isotope is only about 20 minutes. By completing the peptide synthesis with the 11 C-labeled amino acid, peptide 1 can be used immediately after radioactive labeling.
  • the peptide of SEQ ID NO: 1 has the sequence of the CDR3 loop 7 of a TCR 6, which is formed by a T cell of a patient with a diffuse large-cell B-cell lymphoma (DLBCL) (Yin Q et al., 2010).
  • the DLBCL is a Malig ⁇ ne lymph node enlargement, in addition to the normal lymphocytes especially many lymphoblasts are formed. On the basis of the morphology of the lymphoblast, a distinction is made between among others, centroblastic and immunoblastic lymphomas.
  • DLBCL is one of the aggressive non-Hodgkin's lymphomas and occurs at a frequency of approximately 3-5 / 100,000 persons per year.
  • T cells are isolated and expanded in culture.
  • the T cells produce the TCR 6 directed against the HLA antigen complex 20 located on the DLBCL.
  • the clone of a single T cell is used to determine the amino acid sequence of the CDR3
  • ⁇ td is a 11 C-labeled peptide 1, which comprises this sequence on ⁇ and specifically binds to the antigen 4 prepared.
  • the peptide of SEQ ID NO: 1 locates antigen 4 or DLBCL.
  • 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 a peptide 1 therein.
  • the circulatory system 10 comprises various schematically represented organs, such as lung 12, heart 13, liver 14, intestine 15 and kidney 16, and the main arteries 11, which connect these organs.
  • the peptide 1 is represented by triangles along the wires 11.
  • the degradation products 17 of the peptide 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 peptides.
  • the distribution of peptide 1 in the circulatory system 10 comprises four phases, which are listed along the top-down view. Phase I: Peptide 1 is injected into the circulatory system 10 of the organism.
  • Phase II Via the blood circulation system 10, the peptide 1 is transported into the organs 12, 13, 14, 15, and 16 of the organism.
  • Phase III The circulating peptide 1 binds specifically to the antigen 4 and accumulates on the diseased tissue 18 because it presents the HLA-antigen complex 20 with the antigen 4 on its surface.
  • Phase IV Unbound peptide 1 is rapidly metabolised and enzymatically degraded.
  • the organism not failed ⁇ det between own peptides and the peptide 1, because it is composed of amino acids 2, 3, which correspond to the body's own molecules.
  • the degradation products 17 of the peptide of amino acids 1 and 2, 3 collect predominantly they are over the bladder and the ureter excreted ⁇ in the kidney 16 from where.
  • Massoud TF, Gambhir SS Molecular imaging in living subjects: seeing fundamental biological processes in a new light; Genes Dev. 2003 Mar 1; 17 (5): 545-80. 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. 2008 Aug; 19 (8): 1596-603.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Pathology (AREA)
  • Biotechnology (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne l'utilisation d'un peptide (1) pour la production d'un agent destiné à la détection d'un tissu malade (18) qui forme un complexe d'antigènes des leucocytes humains (HLA) (20). Selon l'invention, le peptide (1) comporte une séquence d'acides aminés d'une boucle 3 de région déterminant la complémentarité (CDR) (7) d'un récepteur de cellule T (TCR) (6) dirigé contre le complexe HLA (20), et il se lie à un antigène (4) du complexe HLA (20). Le peptide (1) comprend en outre un atome de carbone 11C. L'invention porte également sur un radiopharmaceutique destiné à la localisation d'un tissu malade (18) qui forme un complexe HLA (20) qui comporte un tel peptide (1).
PCT/EP2011/060448 2010-06-30 2011-06-22 Peptide marqué 11c pour la détection d'un tissu malade WO2012000866A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102010026064.9 2010-06-30
DE201010026064 DE102010026064A1 (de) 2010-06-30 2010-06-30 11C-markiertes Peptid zur Detektion eines krankhaften Gewebes

Publications (1)

Publication Number Publication Date
WO2012000866A1 true WO2012000866A1 (fr) 2012-01-05

Family

ID=44511800

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2011/060448 WO2012000866A1 (fr) 2010-06-30 2011-06-22 Peptide marqué 11c pour la détection d'un tissu malade

Country Status (2)

Country Link
DE (1) DE102010026064A1 (fr)
WO (1) WO2012000866A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001083693A2 (fr) * 2000-04-28 2001-11-08 Glaxo Group Limited Composes ayant une affinite pour le recepteur 2 du facteur de croissance de l'endothelium vasculaire (vegfr-2) et utilisations associees
WO2006017619A2 (fr) * 2004-08-06 2006-02-16 The Regents Of The University Of California Peptides cycliques de liaison a un recepteur et leurs methodes d'utilisation
DE102009035465A1 (de) 2009-07-31 2011-02-03 Daimler Ag Batterie, insbesondere Fahrzeugbatterie
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 (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7312318B2 (en) * 2002-03-01 2007-12-25 Immunomedics, Inc. Internalizing anti-CD74 antibodies and methods of use
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 (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001083693A2 (fr) * 2000-04-28 2001-11-08 Glaxo Group Limited Composes ayant une affinite pour le recepteur 2 du facteur de croissance de l'endothelium vasculaire (vegfr-2) et utilisations associees
WO2006017619A2 (fr) * 2004-08-06 2006-02-16 The Regents Of The University Of California Peptides cycliques de liaison a un recepteur et leurs methodes d'utilisation
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
DE102009035465A1 (de) 2009-07-31 2011-02-03 Daimler Ag Batterie, insbesondere Fahrzeugbatterie

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
FALLER A, SCHÜNKE M: "Der Körper des Menschen", 2008, THIEME-VERLAG
HARTVIG P ET AL: "Kinetics of four <11>C-labelled enkephalin peptides in the brain, pituitary and plasma of Rhesus monkeys", REGULATORY PEPTIDES, ELSEVIER SCIENCE BV, NL, vol. 16, no. 1, 1 December 1986 (1986-12-01), pages 1 - 13, XP023462538, ISSN: 0167-0115, [retrieved on 19861201], DOI: 10.1016/0167-0115(86)90190-4 *
HENRIKSEN G ET AL: "Proof of principle for the use of 11C-labelled peptides in tumour diagnosis with PET", EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, SPRINGER VERLAG, HEIDELBERG, DE, vol. 31, no. 12, 10 August 2004 (2004-08-10), pages 1653 - 1657, XP002383248, ISSN: 1619-7070, DOI: 10.1007/S00259-004-1582-1 *
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
ROCK EP, SIBBALD PR, DAVIS MM, CHIEN YH: "CDR3 length in antigen-specific immune receptors", J EXP MED., vol. 179, no. 1, 1 January 1994 (1994-01-01), pages 323 - 8, XP000647839, DOI: doi:10.1084/jem.179.1.323
YIN Q, TAN H, CHEN S, YANG L, YE J, LI Y: "Characterization of conserved CDR3 sequence of TCR alpha- and beta-chain genes in peripheral blood T-cells from patients with diffuse large B-cell lymphoma", HEMATOLOGY, vol. 15, no. 1, February 2010 (2010-02-01), pages 48 - 57

Also Published As

Publication number Publication date
DE102010026064A1 (de) 2012-01-05

Similar Documents

Publication Publication Date Title
EP1784422B1 (fr) Invention concernant le glp-1 et l&#39;exendine
Kilbourn et al. Positron emission tomography imaging of (2R, 3R)-5-[18F] fluoroethoxybenzovesamicol in rat and monkey brain: a radioligand for the vesicular acetylcholine transporter
EP0606683A2 (fr) Agents pour la diagnose des maladies vasculaires
DE60318466T2 (de) An leukozyten bindende verbindung und diese verbindung im markierten zustand als wirkstoff enthaltende medizinische zusammensetzung
WO2012000866A1 (fr) Peptide marqué 11c pour la détection d&#39;un tissu malade
EP3271374B1 (fr) Peptides se liant spécifiquement à des espèces a-bêta pour la thérapie et/ou le diagnostic de la démence d&#39;alzheimer
DE69839050T2 (de) Bilderzeugungs verfahren und zusammensetzungen
WO2012000861A1 (fr) Aptamère marqué au carbone 11 (11c) permettant de détecter un tissu malade
WO2012000862A1 (fr) Peptide marqué 11c pour la détection d&#39;un tissu malade
WO2012000763A1 (fr) Peptide marqué 11c pour la détection d&#39;un tissu malade exprimant un récepteur igf
EP4034177A1 (fr) Composition de cellules comprenant des cellules souches mésenchymateuses radiomarquées, son utilisation et procédé de préparation de cellules souches mésenchymateuses radiomarquées
WO2012000784A1 (fr) Peptide marqué 11c pour la détection de neurones exprimant un récepteur de l&#39;acétylcholine
AU2003217467A1 (en) Avidin dimers effective in increasing the concentration of radioactive biotin in pretargeted radioimmunotherapy
DE4337599A1 (de) Metallbindende cysteinfreie Peptide für Diagnose und Therapie, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen
WO2012000791A2 (fr) Agent de diagnostic permettant de localiser un tissu malade
WO2012000746A1 (fr) Peptide marqué 11c pour la détection d&#39;un tissu malade exprimant un récepteur de chimiokine
EP1454137B1 (fr) Utilisation d&#39;un ligand marque presentant une specificite pour la molecule cd4 humaine afin d&#39;etablir un diagnostic en vue d&#39;analyser des modeles de migration et/ou de distribution de populations cellulaires
WO2012000843A1 (fr) Peptide marqué au carbone 11 (11c) permettant de détecter un antigène
DE102010026056A1 (de) 11C-markiertes Peptid zur Detektion eines Tumors, der einen Peptidtransporter exprimiert
DE102010026065A1 (de) 11C-markiertes Peptid zur Detektion eines Tumors, der einen Bombesin-Rezeptor exprimiert
DE102010026060A1 (de) 11C-markiertes Peptid zur Detektion eines Tumors, der einen Somatostatinrezeptor exprimiert
DE102010026061A1 (de) 11C-markiertes Peptid zur Detektion eines Tumors, der einen Her2/neu-Rezeptor exprimiert
DE102010026058A1 (de) 11C-markiertes Peptid zur Detektion eines Antikörpers
DE102011118030A1 (de) Herstellung und Verwendung eines Peptids mit einer N-terminalen 11C-markierten Acetylgruppe
DE102010026062A1 (de) Aptamer-Komplex zur Detektion eines krankhaften Gewebes

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11728812

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11728812

Country of ref document: EP

Kind code of ref document: A1