Cyclic-RGD penta-peptides cRGDyK derivatized with cyclopentadienyl complexes of technetium and rhenium as radiopharmaceutical probes.

The present study reports the syntheses of half-sandwich complexes of the type [M(η -C H CONH-R)(CO) ] (M═Re, Tc;R═cyclic RGD peptide (cRGDyK) for potential imaging of α β integrin expression. The Tc complex was prepared directly from the reaction of [ Tc(OH ) (CO) ] with cRGDyK, doubly conjugated to Thiele's acid [(C H COOH) ] in water. This approach extends the viability of metal-mediated retro Diels-Alder reactions for the preparation of small molecules such as linear tripeptides to a more complex cyclic peptide carrying a [(η -C H ) Tc(CO) ] tag. The Diels-Alder product [(C H CONH-cRGDyK) ] was prepared from Thiele's acid via double peptide coupling. The Re-complex [Re(η -C H CONH-cRGDyK)(CO) ] was obtained by attaching [Re(η -C H COOH)(CO) ] directly to the N-terminus of cRGDyK. The identity of the Tc-complex is confirmed by chromatographic comparison with the corresponding rhenium complex, fully characterized by spectroscopic techniques.