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Project List » Development of Functional Radiopharmaceuticals Based on Targeted Peptides for PET Molecular Imaging and Receptor Radionuclide Therapy

Development of Functional Radiopharmaceuticals Based on Targeted Peptides for PET Molecular Imaging and Receptor Radionuclide Therapy
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Acronym: PETER
Contracting Authority: Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI)
Number / Date of the contract: 228 / 2014
Parteneriate, PN-II-PT-PCCA-2013-4-1960
Project Manager: Dr. Dana Niculae
Partners:
Starting date / finishing date: 2014-07-01 / 2016-06-30
Project value: 1250000 RON
Abstract: The understanding of the early mechanisms of diseases, together with the development of new drugs, led to a growing need for novel, sensitive and safe imaging tracers that should facilitate the rapid translation of the results obtained on animal models to medical practice. Molecular imaging probes are a special class of pharmaceuticals that target specific biochemical signatures associated with a certain disease and allow for non-invasive imaging at molecular level. Because changes in biochemistry occur well before diseases reach an advanced stage, molecular imaging probes make it possible to locate and stage a disease, track the effectiveness of a drug, treat the disease, monitor the response and select the patients to allow for more personalized diagnosis and treatment. The anticipated success of personalized medicine will in part depend on a molecular-targeted drug having a linked diagnostic test designed to plan or to monitor therapy in real time as a way to determine its ongoing efficacy. Molecular imaging has the potential to highlight both normal and abnormal biochemical pathways in individual patients. Molecular targets such as hypoxia, angiogenesis, receptor expression on tumor cell surface and metabolism are just a few of the biochemical pathways that are of interest in order to evaluate the cancer detection and the therapy follow-up. Surgery and external radiation therapy are the major treatment modalities for primary tumors and large metastases, but other, complementary methods are needed to achieve improvements in the treatment of disseminated malignant diseases. Radionuclide therapy is based on the same biochemical processes, aiming to locally induce severe DNA-damage and to eradicate disseminated tumor cells and small metastases. The project aims to contribute to improvement of differential diagnosis, prognosis, planning and monitoring of cancer treatment and advancing of the systemic radiotherapy for disseminated malignant diseases. We will investigate new functional radiopharmaceuticals that assess cellular targets with high specificity and efficacy, and allow differential diagnosis, prediction and monitoring of therapeutic response, and better radiation dosimetry for internal radiotherapy. The overall objective is to synthesize and evaluate the potential of novel diagnostic/ therapeutic peptide-based radiopharmaceuticals. The project will focus on peptides, targeting receptors overexpressed in angiogenesis: integrin ?v?3 receptors (RGD-peptides), and on various types of tumor cell surface: somatostatin (octreotide), neurotensin, gastrin releasing peptide (bombesin) and glucagon-like peptide (exendin) receptors. The carriers will be radiolabelled with positron emitters and therapeutic radionuclides 68Ga, 64Cu and 177Lu using bifunctional chelators, resulting in functional radiopharmaceuticals that map the processes in high quality 3D images and allow for quantitative imaging through positron emission tomography (PET), while the beta emitters will deliver high radiation dose with high efficacy and low non-target irradiation. The following specific aims are proposed: (1) Evaluate the interaction of radiolabeled peptides with targeting receptors and improve the specific binding by chemical modifications; (2) Radiolabel the selected peptides with 68Ga, 64Cu and 177Lu; optimizing the labeling and automation of the processes, according to pharmaceutical preparations regulations; (3) in vitro, in vivo and ex vivo biological evaluation; and (4) documentation for clinical trials. The leading compunds will be selected and translated to clinical trials; up to three theranostic agents will be designed for preparation in a GMP facility (at project coordinator). The innovative technologies and products resulted from the project, designed for PET molecular imaging of cancer and angiogenesis and for receptor radionuclide therapy, will be described, demonstrated, communicated in scientific journals and disseminated.

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