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

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 Y-90-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)](2) [DOTA-(RGD)(2)] for in vivo targeted therapy utilizing Y-90 obtained from a novel electrochemical Sr-90/Y-90 generator. The performance of the generator was evaluated to ensure its suitability for providing Y-90 in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. Y-90-DOTA(RGD)(2) was synthesized in high yield (86.2 +/- 2.5%) and radiochemical purity (98.4 +/- 0.5%) using clinically relevant dose (similar to 3.8 GBq) of Y-90. 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 Y-90 labeled cyclic RGD peptides for targeted therapy of tumors overexpressing integrin-alpha(v)beta(3) receptors.