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

Abstract

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.

• Authors: Ekaterina Dadachova, Tiffany Moadel, Andrew D Schweitzer, Ruth A Bryan, Tong Zhang, Lisa Mints, Ekaterina Revskaya, Xianchuan Huang, Geraldina Ortiz, Jerome S Nosanchuk, Joshua D Nosanchuk, Arturo Casadevall
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 21 Issue 2 Pg. 117-29 (Apr 2006) ISSN: 1084-9785 [Print] United States
• PMID: 16706632 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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