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 Y-90-DOTA-Re(Arg(11))CCMSH and Lu-177-DOTA-Re(Arg(11))CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of Y-90-DOTA-Re(Arg(11))CCMSH and Lu-117-DOTA-Re(Arg(11))CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of Y-90-DOTA-Re(Arg(11))CCMSH and Lu-177-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: Y-90-DOTA-Re(Arg(11))CCMSH and Lu-117-DOTA-Re(Arg(11))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 Y-90-DOTA-Re(Arg(11)) CCMSH and Lu-177-DOTA-Re(Arg(11))CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of Y-90-DOTA-Re(Arg(11))CCMSH and Lu-117-DOTA-Re(Arg(11))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 Y-90-DOTA-Re(Arg(11))CCMSH and Lu-177-DOTA-Re(Arg(11))CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations. (c) 2005 Elsevier Inc. All rights reserved.