Département de chimie moléculaire

Angiogenesis plays a central role in tumor growth and metastasis. Quantification or evaluation of angiogenesis is crucial for antiangiogenic therapeutic strategies. Since integrin $\alpha$v$\beta$3 overexpression appears specific of angiogenesis at the adult stage, it became a target of choice over the past decade, and labeled RGD-based compds., therefore, constitute promising agents for noninvasive tumor visualization and targeting. We evaluated the chem. and biol. properties of a new tetrameric RGD-based tracer named RAFT-RGD. RAFT-RGD was radiolabeled with indium-111, using the chelating agent [(1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid] (DOTA). Labeling reaction parameters, such as time, temp., solvent, or molar ratio, were investigated in order to optimize the final properties of the labeled RGD peptide. A 97.7{%} ± 0.7{%} binding efficiency was achieved. 111In-DOTA-RAFT-RGD was injected i.v. in a cohort of $\alpha$v$\beta$3-pos. tumor-bearing nude mice. We noninvasively visualized the in vivo distribution of the tracer, using a small-animal gamma camera. In vivo distribution and stability were also studied after organ removal. In vivo, the radiolabeled peptide showed rapid blood clearance and tumor uptake. Whole-body noninvasive planar imaging allowed tumor visualization from 1 h postinjection. However, renal uptake must be reduced to increase the therapeutic potential of RAFT-RGD. [on SciFinder(R)]