Therapeutic Efficacy of a 177 Lu-Labeled DOTA Conjugated α -Melanocyte-Stimulating Hormone Peptide in a Murine Melanoma-Bearing Mouse Model

Abstract

The aim of this study was to examine the therapeutic efficacy of ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH in the B16/F1 murine melanoma-bearing mouse model. Methods: ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH was prepared in 0.5 M NH₄OAc at a pH of 5.4. Two (2) treatment groups of 10 melanoma-bearing C57 mice were administrated with 2 × 18.5 MBq and 1 × 37.0 MBq of ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH through the tail vein, respectively. One (1) group of 10 melanoma-bearing C57 mice was injected with saline placebos as untreated melanoma-bearing controls. Results: In contrast to the untreated melanomabearing control group, ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH administration yielded rapid and lasting ther-apeutic effects in the treatment groups. ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH treatment decreased the tumor growth rate and significantly (p < 0.05) prolonged the survival time of melanoma-bearing C57 mice. Treatment with 2 × 18.5 MBq or 1 × 37.0 MBq of ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH significantly extended the mean survival of tumor-bearing mice from 13.3 to 15.1 and 16.2 days, respectively. ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH treatment produced no observed acute renal toxicity. Conclusions: The therapy study results revealed that ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH yielded quantitative therapeutic effects in B16/F1 melanoma-bearing mice and appeared to be a promising radiolabeled peptide for the targeted radionuclide therapy of melanoma.