Group leaders: Dominique Le Guludec & François Rouzet
The new team 4 is originated from the very large previous team 3 of U698. Members involved in preclinical and clinical imaging are now gathered in this new team. They are all from Paris 7 University and are affiliated to X. Bichat hospital. The new team is constituted by 3 PU-PH, 4 MCU-PH (one under recruitment), 2 PH (one with contrat d’interface), 3 physicians in nuclear medicine, 2 CCA. Team 4 aims the development of imaging technologies as diagnostic surrogate markers in health and disease. The purpose is to provide early detection and location of the biological process involved in tissue degeneration, and to follow in situ the therapeutic activity of new compounds targeting localized tissue specific diseases. After moving from morphological to functional approaches, the new challenge is to shift to molecular imaging, providing evidence of specific molecular, cellular and tissue localization targeting. Molecular imaging is a high standard tool for translating biological molecular knowledge into clinical applications for all fields of human tissue pathologies. Specific molecular imaging requires developing innovative ligands identified through biological and/or chemical approaches, and transversal multidisciplinary competencies and know-how: chemistry, pathophysiology, animal experimental model validation, pharmacology, imaging, biophysics, radiopharmacology, software. Imaging specialists must be closely associated to the research of such imaging ligands because the development of clinical applications is the final goal. The Unit is offering such a multidisciplinary collaboration, and national or international collaborations help us in some fields were some competencies are lacking, such as signal quantification or PET chemistry.
Since several years, we have developed a translational research going from chemistry to clinical applications of new ligands. We have built an imaging platform in both sides: at the research level, with all imaging modalities dedicated for small animal imaging (7T MRI, SPECT-CT and PET, ultrasound), as well as at the clinical level (1.5 and 3T MRI, 64 time of flight PET-CT, CZT gamma-camera), and all requirements for gamma-emitters and 68Gallium labelling. This platform is now integrated in a national network (FLI), which should help us acquiring soon a SPECT-MRI for multimodality imaging. Our group have also very close collaboration with: 1/ a highly innovative group in the field of functional MRI (R Synkus and B Van Beers, U773), with elaboration of a joint program on multimodality imaging (SPECT-MRI) in the context of the FLI network; this project is not described here but in the SFR project; 2/ IMNC laboratory, CNRS UMR 8165, Irène Buvat), which has a strong expertise on signal quantification in clinical and pre-clinical PET images.
Our project is to develop new ligands targeting biological activities within diseased cardiovascular tissues, such as inflammation, thrombus, ischemia, cell necrosis and apoptosis, fibrosis. Some non-specific agents, such as 18FDG have been evaluated, but there is still room for specific agents. Several targets have been identified; among them three represent complementary approaches: selectins (inflammation), collagen (fibrosis), and serine proteases (neoangiogenesis). We also evaluate new imaging ligands developed by industry in original cardiovascular applications and animal models. Our research includes pre-clinical evaluation on animal models developed by several teams of the unit, human ex-vivo evaluation using the large tissue collection, and clinical evaluation from early clinical stages of proof of concept to large multicentric trials.