Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer

In this study, we reported the preparation and evaluation of ¹⁷⁷Lu-DOTA-RGD2, ¹⁷⁷Lu-DOTA-Bz-RGD2 and ¹⁷⁷Lu-DTPA-Bz-RGD2 (RGD2 = Ec(RGDfK)]₂) as a potential therapeutic radiotracers for the treatment of integrin α_vβ₃-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of ¹⁷⁷Lu-DOTA-RGD2, ¹⁷⁷Lu-DOTA-Bz-RGD2 and ¹⁷⁷Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100°C and higher DOTA-conjugate concentration were needed for successful ¹⁷⁷Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of ¹⁷⁷Lu-labeled cyclic RGDfK peptides, and ¹⁷⁷Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin α_vβ₃-positive tumors.