European Journal of Medicinal Chemistry 2011-05-01

Synthesis, in vitro screening and in vivo evaluation of cyclic RGD analogs cyclized through oxorhenium and oxotechnetium coordination.

Marie Aufort, Marta Gonera, Marie-Anne Lelait, Bertrand Czarny, Loïc Le Clainche, Robert Thaï, Amandine Landra, Mathias Ruinart de Brimont, Christophe Dugave

Index: Eur. J. Med. Chem. 46(5) , 1779-88, (2011)

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Abstract

A library of RGD tripeptide analogs cyclized through oxorhenium coordination by an NS2/S chelation motif was synthesized. Screening towards integrins αVβ3, αIIbβ3 and αVβ5 led to the identification of 6 oxorhenium complexes that bind to integrin αVβ3 in the submicromolar range. In vivo evaluation of five of the corresponding oxotechnetium complexes using nude mice bearing a U87MG human tumor xenograft showed a significant and specific accumulation of radioactivity inside the tumor. The best results in vivo were obtained with complexes Tc-16 and Tc-50 that displayed a higher tumor accumulation and a lower distribution in other tissues relative to a reference cyclopentapeptide tracer.Copyright © 2011 Elsevier Masson SAS. All rights reserved.