Radiolabeled melanin-binding peptides are safe and effective in treatment of human pigmented melanoma in a mouse model of disease

Cancer Biother Radiopharm. 2006 Apr;21(2):117-29. doi: 10.1089/cbr.2006.21.117.


The incidence of melanoma is rising, and therapeutic options for metastatic melanoma are limited. We report the results of experimental melanoma therapy with 188-Rhenium-labeled melanin-binding decapeptide ((188)RE-HYNIC-4B4) and a comprehensive safety evaluation of this treatment. (188)RE-HYNIC- 4B4 bound only to nonviable eumelanotic MNT1 and pheomelanotic SK-28-MEL human melanoma cells in vitro, as determined by immunofluorescence, which is consistent with the inaccessibility of intracellular melanin in live cells, and suggests specificity for tumors with a significant amount of extracellular melanin. Administration of 1 mCi (188)RE-HYNIC-4B4 to MNT1 tumor-bearing mice significantly slowed tumor growth, with the therapeutic effect being a result of specific binding to tumor melanin, as irrelevant (188)RE-labeled decapeptide did not produce therapeutic gain. Repeated doses of (188)RE-HYNIC-4B4 had a more profound effect on tumor growth than a single dose. Treatment of tumors with 0.3-0.4 cm diameter was more effective than of larger ones (0.5-0.7 cm). There was no difference in uptake of (188)REHYNIC- 4B4 in melanized tissues of black C57BL6 mice and no histologically apparent damage to these tissues in comparison with white BALB/C mice. Treatment of C57BL6 mice with (188)RE-HYNIC-4B4 did not change their behavior, as established by SHIRPA protocol, and did not cause damage to neurons and glial cells. These results indicate that radiolabeled melanin-binding peptides are efficient and safe in treatment of melanoma and could be potentially useful against this tumor.

Publication types

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

MeSH terms

  • Animals
  • Brain Diseases / etiology
  • Brain Diseases / pathology
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Fluorescent Antibody Technique / methods
  • Humans
  • Hydrazines / chemistry
  • Hydrazines / therapeutic use
  • Immunotoxins / chemistry
  • Immunotoxins / pharmacokinetics
  • Immunotoxins / therapeutic use*
  • Immunotoxins / toxicity
  • Kidney Diseases / etiology
  • Kidney Diseases / pathology
  • Male
  • Melanins / chemistry
  • Melanins / metabolism*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / radiotherapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nicotinic Acids / chemistry
  • Nicotinic Acids / therapeutic use
  • Peptides / chemical synthesis
  • Peptides / pharmacokinetics
  • Peptides / therapeutic use*
  • Peptides / toxicity
  • Radioimmunotherapy
  • Radioisotopes / pharmacokinetics
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Radiopharmaceuticals / toxicity
  • Rhenium / pharmacokinetics
  • Rhenium / therapeutic use*
  • Rhenium / toxicity
  • Tissue Distribution
  • Xenograft Model Antitumor Assays


  • 6-hydrazinopyridine-3-carboxylic acid
  • Hydrazines
  • Immunotoxins
  • Melanins
  • Nicotinic Acids
  • Peptides
  • Radioisotopes
  • Radiopharmaceuticals
  • Rhenium