Objective
Objectives
The major goal of this project is to develop novel neurotensin (NT) and bombesin/gastrin releasing peptide (BBN/GRP) analogs, that can be tagged with radionuclides appropriate for either diagnostic (PET, SPECT) or therapeutic application. The new peptide based radioagents will be evaluated as new molecular probes for the early in vivo diagnosis and/or therapy of NT or BBN/GRP receptor positive tumors and their metastases.
Neuropeptides are a class of very potent native substances controlling important biological processes through high affinity receptors located on the cell membrane of target cells. After the discovery had been made that a wide spectrum of malignant cells also express high affinity and high density peptide receptors on their surface, neuropeptides have been drawing increasing attention in the Nuclear Medicine world. Their superiority over Monoclonal Antibodies (MoAbs) used so far relies upon their unique biological characteristics, most importantly their rapid and specific localization on target cells in combination with their fast blood clearance. It is therefore their pharmacokinetics as well as target specificity that make them attractive vectors for targeting cancer, a strategy already explored successfully forsomatostatin (SS). Indeed, the in vivo imaging of SS receptors involved in much pathology by radiolabeled SS analogs is a new powerful and fast expanding technique. However, since many frequently occurring and devastating tumors do not express SS receptors, it is imperative to search for alternative neuropeptide receptors expressed by these tumors. Recent evidence reports that such malignant lesions, like small cell lung cancer (SCLC), colon carcinoma and certain meningiomas, express high affinity and density bombes in (BBN) and neurotensin (NT) receptors on the tumor cell membrane. For this reason, BBN and NT are emerging as potential tools for their early diagnosis and therapy. This coordinated project aims at the development of radiolabeled BBN and NT analogs, that are useful either for the scintigraphic localization of BBN and NT receptor positive tumors and their metastases in vivo and/or for receptor associated therapy of these tumors.
For this purpose, peptide based analogs of prolonged plasma life and preserved biological action will be properly modified to incorporate radionuclides of choice. The main non invasive diagnostic modalities in Nuclear Medicine PET (positron emission tomography) and SPECT(single photon emission computerized tomography) require each the application of different radionuclides. Tagging of BBN and NT with the radiohalides 123/and 18F useful for SPECT and PET respectively will be initially pursued, as requiring the least possible alterations of peptide structure and consequently biological action. Modifications of the peptide backbone similar for both radiohalides--like incorporation of Tyr or Trp residues or coupling of aromatic groups at terminal amino acids-- will be attempted to achieve this goal. However, since 99mTc still remains the gold standard of Nuclear Medicine diagnosis using SPECT, suitable chelating systems will be coupled to the N-terminal amino acid of BBN and NT analog, to enable tagging with this metallic radionuclide. Similar modifications will be undertaken for developing a therapeutic receptor seeking agent carrying one of the two rheniumradionuclides 186Re and 188Re, since the Tc and Re chemistries are interrelated. Proper in vitro tests will demonstrate the suitability and effectiveness of these modifications. Eventually, in vivo experiments in healthy and tumor bearing animals will screen selected agents for clinical trials.05 05
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology lung cancer
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences clinical medicine radiology nuclear medicine
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine pharmacology and pharmacy pharmacokinetics
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
01314 Dresden
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.