A novel concept of radiosynthesis of a (99m)Tc-labeled dimeric RGD peptide as a potential radiotracer for tumor imaging.
Radiolabeled Arg-Gly-Asp (RGD) peptides are promising agents for non invasive imaging of αvβ3 expression in malignant tumors. The integrin αvβ3 binding affinity and consequent tumor uptake could be improved when a dimeric RGD peptide is used as the targeting moiety instead of a monomer. Towards this, a novel approach was envisaged to synthesize a (99m)Tc labeled dimeric RGD derivative using a RGD monomer and [(99m)TcN](+2) intermediate. The dithiocarbamate derivative of cyclic RGD peptide G3-c(RGDfK) (G3=Gly-Gly-Gly, f=Phe, K=Lys) was synthesized and radiolabeled with [(99m)TcN](+2) intermediate to form the (99m)TcN-[G3-c(RGDfK)]2 complex in high yield (∼98%). Biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed good tumor uptake [4.61±0.04% IA/g at 30min post-injection] with fast clearance of the activity from non-target organs/tissue. Scintigraphic imaging studies showed visible accumulation of activity in the tumor with appreciable target to background ratio.