Chemical and biological evaluations of an (111)in-labeled RGD-peptide targeting integrin alpha(V) beta(3) in a preclinical tumor model.

摘要: 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 at the adult stage, it became target choice over past decade, labeled RGD-based compounds, therefore, constitute promising agents noninvasive visualization targeting. We evaluated chemical biologic properties new tetrameric tracer named RAFT-RGD. RAFT-RGD was radiolabeled with indium-111, using chelating agent [(1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid] (DOTA). Labeling reaction parameters, such as time, temperature, solvent, molar ratio, were investigated order to optimize final RGD peptide. A 97.7% +/- 0.7% binding efficiency achieved. (111)In-DOTA-RAFT-RGD injected intravenously cohort alpha(v)beta(3)-positive tumor-bearing nude mice. noninvasively visualized vivo distribution tracer, small-animal gamma camera. In stability also studied after organ removal. vivo, peptide showed rapid blood clearance uptake. Whole-body planar imaging allowed from 1 hour postinjection. However, renal uptake must be reduced increase potential