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

A library of RGD tripeptide analogs cyclized through oxorhenium coordination by an NS2/S chelation motif was synthesized. Screening towards integrins αVß3, αIIbß3 and αVß5 led to the identification of 6 oxorhenium complexes that bind to integrin αVß3 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.