Chemical and biological evaluations of an 111in-labeled RGD-peptide targeting integrin alphaV beta3 in a preclinical tumor model.Report as inadecuate




Chemical and biological evaluations of an 111in-labeled RGD-peptide targeting integrin alphaV beta3 in a preclinical tumor model. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Radiopharmaceutiques biocliniques 2 DCM - Département de Chimie Moléculaire

Abstract : Angiogenesis plays a central role in tumor growth and metastasis. Quantification or evaluation of angiogenesis is crucial for antiangiogenic therapeutic strategies. Since integrin alphavbeta3 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. 111In-DOTA-RAFT-RGD was injected intravenously in a cohort of alphavbeta3-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.

Keywords : cancer molecular imaging radiopharmaceuticals





Author: Mitra Ahmadi - Lucie Sancey - Arnaud Briat - Laurent Riou - Didier Boturyn - Pascal Dumy - Daniel Fagret - Catherine Ghezzi - Jea

Source: https://hal.archives-ouvertes.fr/



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