DATABASE-RESEARCH | GROUP OF CLINICAL PATIENT RESEARCH | ||||||
Pr Yann Seimbille | Head of group CV | Research subject | Members of the group |
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Pr Yann Seimbille HUG/Dépt Radiologie Service de médecine nucléaire Rue Gabrielle-Perret-Gentil 4 1211 Genève Suisse Yann.Seimbille@hcuge.ch Tel.: +41 22 372 75 80 Fax: +41 22 372 75 85 Comments Pages updated the 17.11.2015 |
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Cyclotron
Enormous progress in defining the genetic and molecular alterations that occur in cancer has been made during the past two decades and this has catalyzed a shift towards using targeted therapies for
cancer.
Although, use of molecular targeted agents constitutes a major advance over administration of nontargeted drugs, room for development of drugs with even greater selectivity for pathologic cells still exists. Our first aim in this project is to design and develop promising new class of antineoplastic agents, namely, 'supertargeted' drugs (STD) and the corresponding molecular imaging probes to allow non-invasive assessment of the action of the drug. The new drugs are directed against the erbB receptors family (EGFR, HER-2, ErbB-3, and ErbB-4) and integrins ('v'3, '5'1) since they activate many sig¬naling pathways regulating essential cellular functions, such as cell spreading, migration, survival, proliferation and differentiation. An attractive approach to develop the novel therapeutics, following the paradigm of the so-called 'designed multiple ligands (DML)' strategy, is to develop a single chemical entity that is able to exert different actions beneficial in the treatment of neoplastic disorders, namely, to simultaneously combine synergistic effects by inhibition of several altered pathways. These novel polyfunctional molecules certainly open new horizons to treat complex diseases, such as cancers, but they also represent a crucial new class of molecular imaging probes, which can be used to improve productivity in lead optimization and preclinical profiling, to better identify responders to such 'multi-targeted-molecular therapeutics', and finally refine personalized medicine. Thus far, the drug evaluation process has not kept pace with the discoveries in tumor biology. Cancer remains a high unmet medical need, and molecular imaging, which has emerged both as a new tool/technology over the past decade, has the potential to improve the efficiency and cost-effectiveness of preclinical and clinical drug evaluation process. Positron emission tomography (PET) is actually the preferred molecular imaging tool in oncology for its high sensitivity and the tomographic images. Although, molecular imaging could greatly accelerate drug development against cancer, our ability to evaluate these novel targeted therapeutic agents is still limited, mainly due to the lack of appropriate molecular imaging probes. Current synthetic methods and technology appear totally inadequate to produce them. So, our second aim is to establish new, efficient, and universally applicable synthetic strategy to prepare PET imaging agents, and to develop new devices dedicated to the radiolabeling of compounds with short-lived positron emitters. Finally, our last aim is to use noninvasive microPET/CT imaging to assess drug absorption, biodistribution, and metabolism, to provide evidence of the biological activity, and to confirm on-target drug effects. This high-throughput screening of the drugs using molecular imaging cell-based and animal-based assays should aid decisions to select candidates that seem most likely to be successful or to halt the development of drugs that seem likely to ultimately fail. Group's publications High efficiency production and purification of 86Y based on electrochemical separation. APPLIED RADIATION AND ISOTOPES : INCLUDING DATA, INSTRUMENTATION AND METHODS FOR USE IN AGRICULTURE, INDUSTRY AND MEDICINE 2009 vol. 67(4) pp. 523-529 LUKIC D, TAMBURELLA C, BUCHEGGER F, BEYER G.-J., COMOR J, SEIMBILLE Y Evaluation of [(18)F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING. 2008 vol. 35(6) pp. 1089-1099 SU H, SEIMBILLE Y, FERL GZ, BODENSTEIN C, FUEGER B, KIM KJ, HSU YT, DUBINETT SM, PHELPS ME, CZERNIN J, WEBER WA Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors CLINICAL CANCER RESEARCH 2006 vol. 2(19) pp. 5659-5667 SU H, BODENSTEIN C, DUMONT RA, SEIMBILLE Y, DUBINETT S, PHELPS ME, HERSCHMAN H, CZERININ J Impact on estrogen receptor binding and target tissue uptake of [18F]fluorine substitution at the 16alpha-position of fulvestrant (faslodex; ICI 182,780) NUCLEAR MEDICINE AND BIOLOGY 2004 vol. 31(6) pp. 691-698 SEIMBILLE Y, BENARD F, ROUSSEAU J, PEPIN E, ALIAGA A, TESSIER G, VAN LIER JE Research's domains |