WO2012000763A1 - Peptide marqué 11c pour la détection d'un tissu malade exprimant un récepteur igf - Google Patents

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

Info

Publication number
WO2012000763A1
WO2012000763A1 PCT/EP2011/059600 EP2011059600W WO2012000763A1 WO 2012000763 A1 WO2012000763 A1 WO 2012000763A1 EP 2011059600 W EP2011059600 W EP 2011059600W WO 2012000763 A1 WO2012000763 A1 WO 2012000763A1
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
igf
receptor
igf receptor
carbon atom
Prior art date
Application number
PCT/EP2011/059600
Other languages
German (de)
English (en)
Inventor
Ursus KRÜGER
Oliver Lade
Arno Steckenborn
Sylvie Von Werder
Original Assignee
Siemens Aktiengesellschaft
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 filed Critical Siemens Aktiengesellschaft
Publication of WO2012000763A1 publication Critical patent/WO2012000763A1/fr

Links

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
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins

Definitions

  • 11 C-labeled peptide for detection of a pathological tissue ⁇ bes that expresses an IGF receptor
  • biochemical analyzes of blood and other bodily fluids as well as imaging techniques, for example, for the detection of tumors are used.
  • X-ray, ultrasound, and magnetic resonance imaging have been used to localize diseased tissue and ectopic cell aggregates.
  • Newer methods use the increased metabolic activity of tumor cells compared to healthy tissue.
  • the patient is injected with radioactively labeled sugar molecules that accumulate in the tumor cells.
  • the radioactive radiation of these molecules for example, with a gamma camera, for so-called scintigraphy, taken and the Po ⁇ tion of the tumor detected.
  • Biochemically, cancer diseases, as well as other diseases are detected by specific molecules. The presence and amount of these substances in blood or tissue samples of the patient is determined.
  • IGF receptors are transmembrane tyrosine kinase receptors that are composed of four subunits. They are bound and activated by several ligands, including insulin and insulin-like growth factors (IGF) I and II.
  • the binding of the ligand leads to the phosphorylation of the tyrosine kinase, which activates various cellular signaling pathways.
  • the IGF signaling system is important for the control of basic cell functions, such as cell proliferation, differentiation and apoptosis (Gualco E et al., 2009).
  • IGF promotes the growth of cells and organs, both during early development and in the adult organism.
  • the overactivation of this signaling pathway leads to the fact that the affected cells do not die off and continue to proliferate. Accordingly, in biopsies of malignant tumors increased amounts of IGF receptors are regularly detected.
  • cancer therapies are being developed that specifically interfere with the IGF signaling system (Law J et al., 2008).
  • IGF receptors Excessive expression of IGF receptors is an indicator of both the malignancy of a tumor and the formation of metastases (Zhang C et al., 2010), and thus an unfavorable disease prognosis. Therefore, it is of great medical importance ⁇ SSSR determine early on whether and if so how many cells of a tumor expressing an IGF receptor. In addition, there is a need to be able to detect IGF receptor-positive metastases early. The invention is therefore based on the object, a cost-effective and well-tolerated for the patient agent for detecting a diseased tissue that expresses an IGF receptor provide. This task is done by the
  • a peptide for the production of an agent for detecting a diseased tissue expressing an IGF receptor.
  • the agent can be produced inexpensively and, well comparable metabolized in the organisms ⁇ mechanism in which the diseased tissue is detected.
  • peptide refers to an organic compound of at least two linked via a peptide bond
  • Amino acids includes both oligopeptides of up to about ten amino acids, polypeptides up to about 50 Amino Text ⁇ reindeer, as well as proteins of up to 150 amino acids, regardless of their primary, secondary or tertiary structure. In this case, both naturally occurring and biotechnologically or synthetically produced compounds are included.
  • the peptide used in the invention is chosen so that it binds to the IGF receptor. Suitable for this are antibodies, their fragments and other polypeptides which bind to the IGF receptor. By their specific binding to the IGF receptor, the peptides can be used to detect diseased tissues that form the IGF receptor.
  • the peptide is chosen so that the bond between the peptide and the receptor IGF-called a linear coefficient. KD value of ⁇ 100 nM, preferably ⁇ 10 nM, more be ⁇ vorzugt of 7.5 nM comprising ,
  • the peptide itself is acids from amino ⁇ , that is constructed from autologous or body like molecules, making it very well comparable to the patient is tolerable. It is not toxic and can be natural
  • 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, hypertrophic 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 receptors for growth factors. These receptors are located on the cell surface and can be bound there by the peptide used according to the invention. IGF receptors are expressed by a variety, especially malignant, tumors.
  • tumors of the pancreas, lung and rectum were, among others, in tumors of the pancreas, lung and rectum, as well as among different ⁇ 's brain tumors, especially in children, demonstrated (Gualco E et al., 2009, Kim SY et al., 2009).
  • the peptide used in the invention such tumors can be iden ⁇ tified localized and reliable, without an invasive procedure to biopsy requires.
  • metastases of such tumors can be detected, provided that they also form the IGF receptor.
  • positrons also referred to as ⁇ + radiation
  • ⁇ + radiation push the positron on an electron, they form two photons away at an angle of 180 °, which is exactly opposite in ge ⁇ modifying the direction of each other.
  • the photons can be detected and used to calculate the position of the positron emission, or of the 11 C carbon atom.
  • the integra- tion of a C-carbon atom in the peptide used in the invention makes it possible to avoid the use of chemical kör ⁇ perfremder substances.
  • ⁇ C carbon isotope into the peptide results in radioactive labeling without complexing agents, such as diethylenetriaminepentaacetate (DTPA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). or ethylenediamine tetraacetate (EDTA), possible.
  • DTPA diethylenetriaminepentaacetate
  • DOSA 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
  • EDTA ethylenediamine tetraacetate
  • a radioactive foreign substance such as 18 fluorine, 133 xenon, or 68 gallium
  • both the presence and the position of the IGF receptor can be detected and mapped. Furthermore, the amount of peptides located at a particular site can also be quantified.
  • Another advantage of the peptide directly labeled with X1 C lies in the favorable signal / background ratio during detection. The peptide binds specifically to the IGF receptor and forms a stable complex with it. Free, unbound peptides, on the other hand, are rapidly metabolized and excreted from the organism because they can be rapidly degraded by endogenous enzymes. This creates a strong and specific signal at the position of the IGF receptor, and the background signal is minimized.
  • the peptide has at least one D-amino acid.
  • 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 made up of amino acids in ⁇ L-configuration.
  • most natural proteases and peptidases work stereoselectively and mainly metabolize 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 determine the half-life of a protein or peptide to ver ⁇ lengthen by even D-amino acids are used in addition to L-amino acids (Neundorf I et al., 2008). As a result, the pharmacological clearance, ie the time until the peptide is eliminated from the organism, can be positively influenced.
  • the terminal amino group of the peptide may be replaced by an isonitrile group.
  • Such modes ⁇ fication reduces, mediated by the amino group of an interaction with proteolytic enzymes without altering the bond between the peptide used in the invention and the IGF receptor.
  • the peptide is an antagonist of the IGF receptor.
  • IGF receptors ⁇ the usually activated by the binding of insulin or insulin-like growth factors to produce approximately phosphorylation cascades are initiated in the cell.
  • the peptide binds to the IGF receptor without triggering its autophosphorylation.
  • the agent is a radiopharmaceutical.
  • radiopharmaceuticals refers to medicines containing radionuclides whose radiation is used for diagnosis and therapy. The most important fields of application are oncology, cardiology and neurology as well as drug research.
  • radionuclides are gamma or beta radiation emitting nuclides, for example Xenon 133, "technetium, gallium 68, fluorine 18 and used. They are usually about Kom ⁇ formers such as DOTA, DTPA or EDTA on mono- or polysaccharides
  • the nuclides will be, depending on the nature of their
  • Radiopharmaceuticals can cause side effects such as anaphylactic or allergic Reaktio ⁇ nen, in the body of a patient.
  • the use of a peptide from the body's own amino acids reduces this risk significantly, because neither the peptide itself, nor its Ab ⁇ building products are toxic.
  • carbon is, in contrast to technetium or xenon, an element found in the body that can naturally be metabolized.
  • the diseased tissue expresses increased amounts of the IGF receptor.
  • the cells Various ⁇ ner tumors carry particularly high levels of IGF receptors on their surface. These include, for example, lung, breast, and pancreatic cancers, sarcomas, and pediatric gastrointestinal stromal tumors.
  • the IGF receptor is an IGF-1 receptor.
  • the family of IGF receptors includes the IGF-1 receptor, the IGF-2 receptor, as well as two insulin receptors (IR), IR-A and IR-B.
  • the IGF-1 receptor is produced in increased amounts by many malignant tumor types and is not limited to ulcers of certain tissues. Therefore, an agent having a peptide which binds to the IGF-1 receptor is useful for the detection and localization of many different diseased tissues, particularly tumor tissues.
  • the IGF-2 receptor has so far been mainly detected on adenocarcinomas of the esophagus and the gastrointestinal tract.
  • the C-carbon atom is the 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 from the peptide, as it would be possible at about a 39ket ⁇ th one of the amino acids.
  • the C-carbon atom is the carbonyl carbon atom of N-terminal amino acid of the peptide.
  • This embodiment is particularly preferred because the peptide immediately after the on ⁇ bring the 11 C-labeled amino acid can be used.
  • 11 C-carbon has ten a half-life of only about 20 for minutes, so that the radiation dose to be selected the higher, the more time between the synthesis of the peptide and be ⁇ ner is situated. 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.
  • Another object of the invention is a radiopharmaceutical comprising a peptide having an 11 C carbon atom for the localization of a tumor expressing an IGF receptor.
  • the radiopharmaceutical invention provides an economical and medically beneficial agent to to determine the posi ⁇ tion of a tumor that expresses an IGF receptor in vivo.
  • the peptides contained therein are distributed within the body and specifically bind to IGF receptors. There- They accumulate on the cells of the tumor where they are detected by the radioactive signal of the 11 C carbon atom. In this way, the position of the tumor and ge ⁇ give if the true loading of metastases in the body of the patient.
  • 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. In contrast to the usual scintigraphic chromatography method, is by the annular configuration of the PET detectors a more precise spatial localization of the positron ⁇ nenemission and thus a substantially more accurate and detailed ⁇ profiled illustration of a diseased tissue or tumor possible. PET also makes it possible to quantify the amount of labeled molecules in a tissue.
  • Also disclosed is a method of localizing a tumor in an organism expressing an IGF receptor comprising the steps of a) providing a peptide, b) administering the peptide to the organism, and c) detecting the peptide in the organism using positron emission tomography (PET).
  • PET positron emission tomography
  • the peptide binds to the IGF receptor and has an 11 C carbon atom.
  • a peptide IGF receptor in the interior of an organism is detected and lenti ⁇ Siert, so that the distribution of the IGF receptor may be observed in the body ei ⁇ nes patient. In this way, the size or extent of a tumor expressing the IGF receptor 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. 1 shows schematically the binding between a peptide 1 and an IGF receptor 4.
  • Peptide 1 comprises 27 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 (*).
  • a portion of the peptide 1 is attached to the IGF receptor 4, which is located on the surface of a Tu ⁇ mors 18.
  • the ⁇ C-labeled peptide 1 binds specifically to the IGF receptor 4, but not to other molecules. Peptide 1 can therefore be used to detect the tumor expressing the IGF receptor 4. The emitted during the decay of the X1 C- carbon atom positrons are detected by positron emission tomography (PET). The location of the positron emission corresponds to the location of the peptide 1 and the IGF receptor 4 bound thereto. The peptide 1 can therefore be used to determine the position of the tumor 18 which forms the IGF receptor 4. To localize a tumor 18 as part of a cancer diagnosis, a patient is administered a radiopharmaceutical containing the 11 C-labeled peptide 1.
  • the peptide 1 binds specifically to the IGF receptor 4 and thus accumulates on the tumor 18, which forms the IGF receptor 4. This accumulation is visualized by PET and determines the distribution of the IGF receptor 4 or the location of the tumor 18 in the body of the patient.
  • the medication of a therapeutic for example, amount of drug and administration plan, according to the position, size and distribution of Tu ⁇ mors 18 are adjusted.
  • FIG. 2 shows a representation of a peptide having the sequence SEQ ID NO: 1 by means of a chemical formula.
  • the peptide of SEQ ID NO: 1 comprises 27 amino acids 2 of the following sequence: serine-phenylalanine-tyrosine-serine-cysteine-leucine-glutamic acid-serine-leucine-valine-asparagine-glycine-prolol-alanine-glutamic acid-lysine Serine-arginine-glycine-glutamine-tryptophan-aspartic acid-glycine-cysteine-arginine-lysine-lysine.
  • N-terminal amino acids 2 serine and phenylalanine are represented by structural formula, 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 the N-terminal serine is an X1 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 11 C carbon isotope is only about 20 minutes. Thereby, That the peptide synthesis is completed with the C-labeled amino acid 3, the peptide 1 can be used immediately after the radioactive label.
  • the peptide of SEQ ID NO: 1 binds specifically to the IGF-1 receptor 4 (US 7,173,005 B2). This receptor is present in large quantities on the surface of cells of colon rectal tumors.
  • the natural ligands of IGF-1 receptor 4 include insulin, IGF-I and IGF-II, among others.
  • the peptide of SEQ ID NO: 1 also binds to the IGF-1 receptor 4 and is therefore suitable for the detection of an IGF-I receptor 4 expressing tissue.
  • a mark by X1 C Carbon is particularly suitable because it does not affect the phy ⁇ si Vietnamese structure of the peptide 1 and neither the affected tissue distribution and tolerability of the peptide. 1
  • 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 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 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 ⁇ .
  • To the left of the center of the circulatory system 10 is additionally shown a pathological tissue 18 with IGF receptors 4, to which peptides 1 are increasingly attached.
  • 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 IGF receptor 4 and accumulates on the diseased tissue 18 because it produces the IGF receptor 4.
  • 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 lekülen Mo.
  • 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.

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 exprime un récepteur de facteur de croissance insulino-semblable (récepteur IGF) (4). Le peptide se lie au récepteur IGF (4) et il comprend un atome de carbone 11C. L'invention porte également sur un radiopharmaceutique destiné à la localisation d'une tumeur (18) qui exprime un récepteur IGF (4). Ce radiopharmaceutique comporte un peptide (1) qui se lie au récepteur IGF (4) et comporte un atome de carbone 11C.
PCT/EP2011/059600 2010-06-30 2011-06-09 Peptide marqué 11c pour la détection d'un tissu malade exprimant un récepteur igf WO2012000763A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102010026052.5 2010-06-30
DE201010026052 DE102010026052A1 (de) 2010-06-30 2010-06-30 11C-markiertes Peptid zur Detektion eines krankhaften Gewebes, das einen IGF-Rezeptor exprimiert

Publications (1)

Publication Number Publication Date
WO2012000763A1 true WO2012000763A1 (fr) 2012-01-05

Family

ID=44627110

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2011/059600 WO2012000763A1 (fr) 2010-06-30 2011-06-09 Peptide marqué 11c pour la détection d'un tissu malade exprimant un récepteur igf

Country Status (2)

Country Link
DE (1) DE102010026052A1 (fr)
WO (1) WO2012000763A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012106556A2 (fr) 2011-02-02 2012-08-09 Amgen Inc. Méthodes et compositions associées à l'inhibition d'igf-1r

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7173005B2 (en) 1998-09-02 2007-02-06 Antyra Inc. Insulin and IGF-1 receptor agonists and antagonists
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 (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070269375A1 (en) * 2003-07-24 2007-11-22 Bracco Imaging S.P.A. Stable Radiopharmaceutical Compositions and Methods for Preparation
WO2010066380A1 (fr) * 2008-12-12 2010-06-17 Bayer Schering Pharma Aktiengesellschaft Composés de triaryl-sulphonium, kit et procédé pour étiqueter des isotopes émettant des positrons

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7173005B2 (en) 1998-09-02 2007-02-06 Antyra Inc. Insulin and IGF-1 receptor agonists and antagonists
DE102009035645A1 (de) 2009-07-29 2011-02-03 Siemens Aktiengesellschaft Verfahren zur Herstellung eines radioaktiv markiertren Peptids
WO2011012414A1 (fr) * 2009-07-29 2011-02-03 Siemens Aktiengesellschaft Procédé de fabrication d'un peptide radiomarqué
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 (12)

* Cited by examiner, † Cited by third party
Title
FALLER A, SCHÜNKE M: "Der Körper des Menschen", 2008, THIEME
FALLER A, SCHÜNKE M: "Der Körper des Menschen", 2008, THIEME-VERLAG
GUALCO E, WANG JY, DEL VALLE L, URBANSKA K, PERUZZI F, KHALILI K, AMINI S, REISS K: "IGF-IR in neuroprotection and brain tumors", FRONT BIOSCI., vol. 14, 1 January 2009 (2009-01-01), pages 352 - 75
H ZHANG ET AL: "Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore", BRITISH JOURNAL OF CANCER, vol. 101, no. 1, 7 July 2009 (2009-07-07), pages 71 - 79, XP055009524, ISSN: 0007-0920, DOI: 10.1038/sj.bjc.6605103 *
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 *
KIM SY, TORETSKY JA, SCHER D, HELMAN LJ: "The role of IGF-1R in pediatric malignancies", ONCOLOGIST., vol. 14, no. 1, January 2009 (2009-01-01), pages 83 - 91
LAW JH, HABIBI G, HU K, MASOUDI H, WANG MY, STRATFORD AL, PARK E, GEE JM, FINLAY P, JONES HE: "Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival", CANCER RES., vol. 68, no. 24, 15 December 2008 (2008-12-15), pages 10238 - 46
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
NAGREN K ET AL: "The synthesis of the neuropeptide Met-enkephalin and two metabolic fragments labelled with <11>C in the methionine methyl group", APPLIED RADIATION AND ISOTOPES, INTERNATIONAL JOURNAL OFRADIATION APPLICATIONS AND INSTRUMENTATION, PART A, PERGAMON PRESS LTD, GB, vol. 37, no. 6, 1 January 1986 (1986-01-01), pages 537 - 539, XP024725671, ISSN: 0883-2889, [retrieved on 19860101], DOI: 10.1016/0883-2889(86)90162-0 *
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
X. TIAN ET AL: "PET Imaging of CCND1 mRNA in Human MCF7 Estrogen Receptor Positive Breast Cancer Xenografts with Oncogene-Specific [64Cu]Chelator-Peptide Nucleic Acid-IGF1 Analog Radiohybridization Probes", THE JOURNAL OF NUCLEAR MEDICINE, vol. 48, no. 10, 1 October 2007 (2007-10-01), pages 1699 - 1707, XP055009526, ISSN: 0161-5505, DOI: 10.2967/jnumed.107.042499 *
ZHANG C, HAO L, WANG L, XIAO Y, GE H, ZHU Z, LUO Y, ZHANG Y, ZHANG Y: "Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer", BMC CANCER., vol. 10, no. 1, 7 May 2010 (2010-05-07), pages 184

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012106556A2 (fr) 2011-02-02 2012-08-09 Amgen Inc. Méthodes et compositions associées à l'inhibition d'igf-1r

Also Published As

Publication number Publication date
DE102010026052A1 (de) 2012-01-05

Similar Documents

Publication Publication Date Title
EP1784422B1 (fr) Invention concernant le glp-1 et l&#39;exendine
DE202014011593U1 (de) Markierte Inhibitoren des prostataspezifischen Membranantigens (PSMA), deren Verwendung als bildgebende Mittel und pharmazeutische Wirkstoffe für die Behandlung von Prostatakrebs
WO2012000763A1 (fr) Peptide marqué 11c pour la détection d&#39;un tissu malade exprimant un récepteur igf
AT405906B (de) Radiomarkierte somatostatin rezeptor-liganden zur diagnose und therapie
WO1995012613A1 (fr) Peptides capables de liaison avec les metaux et sans cysteine pour le diagnostic et le traitement, procedes pour leur preparation et compositions pharmaceutiques contenant ces composes
DE102010026053A1 (de) 11C-markiertes Peptid zur Detektion von Neuronen, die einen Acetylcholinrezeptor exprimieren
WO2012000746A1 (fr) Peptide marqué 11c pour la détection d&#39;un tissu malade exprimant un récepteur de chimiokine
WO2012000764A1 (fr) Peptide marqué 11c pour la détection d&#39;une tumeur exprimant un récepteur de la bombésine
DE102010026061A1 (de) 11C-markiertes Peptid zur Detektion eines Tumors, der einen Her2/neu-Rezeptor exprimiert
EP0772633B1 (fr) Complexes destines au diagnostic de maladies vasculaires
WO2012000781A2 (fr) Peptide marqué au carbone 11 (11c) permettant de détecter une tumeur qui exprime un récepteur de somatostatine
DE102010026057A1 (de) Diagnostikum zur Lokalisation eines krankhaften Gewebes
DE102010026066A1 (de) 11C-markiertes Aptamer zur Detektion eines krankhaften Gewebes
DE102010026056A1 (de) 11C-markiertes Peptid zur Detektion eines Tumors, der einen Peptidtransporter exprimiert
WO2012000862A1 (fr) Peptide marqué 11c pour la détection d&#39;un tissu malade
DE102010026064A1 (de) 11C-markiertes Peptid zur Detektion eines krankhaften Gewebes
DE102010026058A1 (de) 11C-markiertes Peptid zur Detektion eines Antikörpers
US20240066157A1 (en) Molecular imaging complex for positron emission tomography
WO2012000843A1 (fr) Peptide marqué au carbone 11 (11c) permettant de détecter un antigène
DE102011118030A1 (de) Herstellung und Verwendung eines Peptids mit einer N-terminalen 11C-markierten Acetylgruppe
DE112011105133T5 (de) Octapeptid zur Herstellung von radiopharmazeutischen Mitteln, das auf dessen Basis hergestellte Arzneimittel und Diagnoseverfahren von Somatostatin-Rezeptor exprimierenden Tumoren
DE102010026062A1 (de) Aptamer-Komplex zur Detektion eines krankhaften Gewebes
Behe et al. Combination of radiological and nuclear medical imaging in animals: an overview about today's possibilities
WO2003050499A2 (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
Gil-Iceta Targeted Polymeric Nanoparticles: Radiolabelling with GA-67 and in vivo evaluation in a mouse model of pancreatic adenocarcinoma using single photon emission computerized tomography

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: 11725719

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: 11725719

Country of ref document: EP

Kind code of ref document: A1