MOLECULAR NUCLEAR IMAGING OF TUMORAL ANGIOGENESIS USING A RGDCONTAINING TRACER, RAFT-RGD, TARGETED AT THE NEOVESSEL-SPECIFIC INTEGRIN αVβ3. ; ÉVALUATION D'UN RADIOLIGAND DE L'INTÉGRINE αVβ3 (RAFT-RGD) POUR L'IMAGERIE MOLÉCULAIRE DE L'ANGIOGENÈSE TUMORALE.

Tumoral neoangiogenesis targeting is currently a major field of research for the diagnostic and treatment of solid tumors. Endothelial cells from neovessels overexpress several specific markers such as the avb3 integrin, which binds RGD (-Arg-Gly-Asp-)-containing peptides. We evaluated the potential of a novel radiotracer – RAFT-RGD – for the molecular nuclear imaging of neovessels. In vitro, the coupling of 4 c(RGDfK) to the RAFT platform resulted in an increased cellular uptake of the tracer by avb3 positive cells when compared to c(RGDfK). Furthermore, RAFTRGD has a higher affinity than c(RGDfK) and similar properties for angiogenesis inhibition. In vivo, both avb3 positive and negative tumors were visible by non invasive whole body planar and tomographic imaging from 30 min to 24 h post-injection, using a gamma camera dedicated to small animal imaging. Despite a lack of significant contrast improvement compare with c(RGDfK), RAFT-RGD could represent a promising tracer for tumoral angiogenesis since it could provide invaluable information about tumor development and treatment efficacy in Nuclear Medicine departments. Furthermore, thanks to its chemical structure, RAFT-RGD can be labelled with a variety of radioisotopes including γ and b- emitters, allowing interesting therapeutical applications such as internal targeted radiotherapy. ; Le ciblage de la néoangiogenèse tumorale est une voie actuelle de recherche pour le diagnostic et pour le traitement des tumeurs solides. Les cellules endothéliales des néovaisseaux tumoraux surexpriment certains marqueurs spécifiques tels que l'intégrine avb3, qui reconnaît spécifiquement les peptides possédant le motif « RGD » (-Arg-Gly Asp-). Nous avons étudié le potentiel d'un nouveau radiotraceur - le RAFT-RGD - en vue d'imagerie moléculaire nucléaire des néovaisseaux. In vitro, le couplage de 4 c(RGDfK) au RAFT augmente la captation du traceur par les cellules avb3 positives, par rapport au c(RGDfK). De plus, le RAFT-RGD possède une meilleure affinité que le c(RGDfK) et ...