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

Nucl Med Biol. 2005 Jul;32(5):485-93. doi: 10.1016/j.nucmedbio.2005.03.007.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Lutetium / pharmacokinetics*
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / radiotherapy
  • Mice
  • Mice, Inbred C57BL
  • Radiopharmaceuticals / pharmacokinetics*
  • Radiopharmaceuticals / therapeutic use
  • Yttrium Radioisotopes / pharmacokinetics*
  • alpha-MSH / pharmacokinetics*

Substances

  • Radiopharmaceuticals
  • Yttrium Radioisotopes
  • alpha-MSH
  • Lutetium