Therapeutic efficacy of a 177Lu-labeled DOTA conjugated alpha-melanocyte-stimulating hormone peptide in a murine melanoma-bearing mouse model

Cancer Biother Radiopharm. 2007 Jun;22(3):333-41. doi: 10.1089/cbr.2007.376.A.

Abstract

The aim of this study was to examine the therapeutic efficacy of (177)Lu-DOTA-Re(Arg(11))CCMSH in the B16/F1 murine melanoma-bearing mouse model.

Methods: (177)Lu-DOTA-Re(Arg(11))CCMSH was prepared in 0.5 M NH(4)OAc at a pH of 5.4. Two (2) treatment groups of 10 melanoma-bearing C57 mice were administrated with 2 x 18.5 MBq and 1 x 37.0 MBq of (177)Lu-DOTA-Re(Arg(11))CCMSH through the tail vein, respectively. One (1) group of 10 melanoma-bearing C57 mice was injected with saline placebos as untreated melanoma-bearing controls.

Results: In contrast to the untreated melanoma-bearing control group, (177)Lu-DOTA-Re(Arg(11))CCMSH administration yielded rapid and lasting therapeutic effects in the treatment groups. (177)Lu-DOTA-Re(Arg(11))CCMSH treatment decreased the tumor growth rate and significantly (p > 0.05) prolonged the survival time of melanoma-bearing C57 mice. Treatment with 2 x 18.5 MBq or 1 x 37.0 MBq of (177)Lu-DOTA-Re(Arg(11))CCMSH significantly extended the mean survival of tumor-bearing mice from 13.3 to 15.1 and 16.2 days, respectively. (177)Lu-DOTA-Re(Arg(11))CCMSH treatment produced no observed acute renal toxicity.

Conclusions: The therapy study results revealed that (177)Lu-DOTA-Re(Arg(11))CCMSH yielded quantitative therapeutic effects in B16/F1 melanoma-bearing mice and appeared to be a promising radiolabeled peptide for the 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
  • Arginine
  • Chelating Agents
  • Disease Models, Animal
  • Heterocyclic Compounds, 1-Ring
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / radiation effects
  • Lutetium / therapeutic use*
  • Lutetium / toxicity
  • Melanoma / diagnostic imaging
  • Melanoma / drug therapy
  • Melanoma / radiotherapy*
  • Mice
  • Radiography
  • Radioisotopes
  • Survival Analysis
  • alpha-MSH / therapeutic use*

Substances

  • Chelating Agents
  • Heterocyclic Compounds, 1-Ring
  • Radioisotopes
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • alpha-MSH
  • Lutetium
  • Arginine