Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

Nucl Med Biol. 2006 Aug;33(6):723-33. doi: 10.1016/j.nucmedbio.2006.06.005.

Abstract

Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of (90)Y- and (177)Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys(3,4,10), d-Phe(7), Arg(11)]alpha-melanocyte stimulating hormone(3-13) {DOTA-Re(Arg(11))CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence.

Methods: A new peptide of DOTA-Re(Glu(2), Arg(11))CCMSH was designed, synthesized and labeled with (90)Y and (177)Lu. Pharmacokinetics of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice.

Results: (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH exhibited significantly (P<.05) less renal uptake values than (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH were 28.16% and 28.81% of those of (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH, respectively, at 4 h postinjection. (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH displayed higher tumor-to-kidney uptake ratios than (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH was 2.28 and 1.69 times of (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH, respectively, at 4 h postinjection. The (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH activity accumulation was low in normal organs except for kidney.

Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

Publication types

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

MeSH terms

  • Animals
  • Kidney / metabolism*
  • Lutetium*
  • Melanoma / radiotherapy
  • Mice
  • Mice, Inbred C57BL
  • Radioisotopes*
  • Radiopharmaceuticals / pharmacokinetics*
  • Tissue Distribution
  • Yttrium Radioisotopes*
  • alpha-MSH / analogs & derivatives
  • alpha-MSH / pharmacokinetics*

Substances

  • Radioisotopes
  • Radiopharmaceuticals
  • Yttrium Radioisotopes
  • alpha-MSH
  • Lutetium