Tumor-targeting properties of ⁹⁰Y- and ¹⁷⁷Lu-labeled α-melanocyte stimulating hormone peptide analogues in a murine melanoma model

The purpose of this study was to compare the tumor-targeting properties of ⁹⁰Y-DOTA-Re(Arg¹¹)CCMSH and ¹⁷⁷Lu-DOTA- Re(Arg¹¹)CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of ⁹⁰Y-DOTA-Re(Arg¹¹)CCMSH and ¹⁷⁷Lu-DOTA- Re(Arg¹¹)CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of ⁹⁰Y-DOTA-Re(Arg¹¹)CCMSH and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: ⁹⁰Y-DOTA-Re(Arg ¹¹)CCMSH and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of ⁹⁰Y-DOTA-Re(Arg¹¹)CCMSH and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of ⁹⁰Y-DOTA-Re(Arg ¹¹)CCMSH and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH were 25.70±4.64 and 14.48±0.85 %ID/g at 2 h, and 14.09±2.73 and 17.68±3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of ⁹⁰Y-DOTA-Re(Arg¹¹)CCMSH and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations.