Tumor-targeting properties of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues in a murine melanoma model.
The purpose of this study was to compare the tumor-targeting properties of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH in a murine melanoma mouse model.


METHODS
The in vitro properties of cellular internalization and retention of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice.


RESULTS
(90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-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 (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-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 (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations.
Miao
Yubin
Y
Department of Internal Medicine, University of Missouri-Columbia, 65211, USA. miaoy@missouri.edu
Hoffman
Timothy J
TJ
Quinn
Thomas P
TP
D000818:Animals; D005260:Female; D008187:Lutetium / Q000493:pharmacokinetics*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics*; D000521:alpha-MSH / Q000493:pharmacokinetics*
D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D000521:alpha-MSH; D008187:Lutetium