title: Chemical and biological evaluations of an (111)in-labeled RGD-peptide targeting integrin alpha(V) beta(3) in a preclinical tumor model.
abstract: 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 compounds, therefore, constitute promising agents for noninvasive tumor visualization and targeting. We evaluated the chemical and biologic 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, temperature, 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. (111)In-DOTA-RAFT-RGD was injected intravenously in a cohort of alpha(v)beta(3)-positive 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 hour postinjection. However, renal uptake must be reduced to increase the therapeutic potential of RAFT-RGD.
authors.affiliation: INSERM, Radiopharmaceutiques Biocliniques, La Tronche, France.
authors.forename: Mitra
authors.initials: M
authors.lastname: Ahmadi
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.forename: Arnaud
authors.initials: A
authors.lastname: Briat
authors.forename: Laurent
authors.initials: L
authors.lastname: Riou
authors.forename: Didier
authors.initials: D
authors.lastname: Boturyn
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Daniel
authors.initials: D
authors.lastname: Fagret
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vuillez
mesh_terms: D000818:Animals; D005260:Female; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid