Synthesis and in vivo evaluation of Tc-99m-labeled cyclic CisoDGRC peptide conjugates for targeting αvβ3 integrin expression

Two alpha(v)beta(3) integrin-binding peptide conjugates containing the cyclic CisoDGRC motif, a linker, and a chelator to enable Tc-99m labeling via the fac-[Tc-99m(CO)(3)](+) core were synthesized. In vivo biodistribution studies in U87MG tumor-bear nude mice at 1 h post-injection revealed a profound effect of the linker on the clearance of the radiotracer from the blood stream. In vivo blocking studies demonstrated the selective binding to the tumors expressing alpha(v)beta(3)-integrin and other tissues. The HPLC analysis of urine samples collected upon necropsy showed no degradation indicating their metabolic stability. These results suggest that cyclic CisoDGRC motif could be exploited as a new alpha(v)beta(3)-targeting vector by an appropriate selection of a linker between the peptide and the payload to obtain optimum pharmacokinetic properties. (c) 2010 Elsevier Ltd. All rights reserved.