Utilization of a novel electrochemical 90Sr/90Y generator for the preparation of 90Y-labeled RGD peptide dimer in clinically relevant dose

Abstract

Abstract The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dose of 90Y-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)]2 [DOTA-(RGD)2] for in vivo targeted therapy utilizing 90Y obtained from a novel electrochemical 90Sr/90Y generator. The performance of the generator was evaluated to ensure its suitability for providing 90Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. 90Y-DOTA-(RGD)2 was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∼3.8 GBq) of 90Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing 90Y labeled cyclic RGD peptides for targeted therapy of tumors over-expressing integrin-α v β 3 receptors.