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

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

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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 (188RE-HYNIC- 4B4) and a comprehensive safety evaluation of this treatment. 188RE-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 188RE-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 188RE-labeled decapeptide did not produce therapeutic gain. Repeated doses of 188RE-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 188RE-HYNIC-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 188RE-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.

Original languageEnglish (US)
Pages (from-to)117-129
Number of pages13
JournalCancer Biotherapy and Radiopharmaceuticals
Volume21
Issue number2
DOIs
StatePublished - 2006

Fingerprint

Melanins
Melanoma
Peptides
Neoplasms
Therapeutics
Inbred BALB C Mouse
Rhenium
Experimental Melanomas
Investigational Therapies
Therapeutic Uses
Growth
Neuroglia
Fluorescent Antibody Technique
Safety
Neurons
Incidence

Keywords

  • 188-Rhenium
  • Melanin
  • Melanin-binding peptide
  • Melanoma
  • Nude mice
  • Radiolabeled peptides
  • Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Radiolabeled melanin-binding peptides are safe and effective in treatment of human pigmented melanoma in a mouse model of disease. / Dadachova, Ekaterina; Moadel, Tiffany; Schweitzer, Andrew D.; Bryan, Ruth A.; Zhang, Tong; Mints, Lisa; Revskaya, Ekaterina; Huang, Xianchuan; Ortiz, Geraldina; Nosanchuk, Jerome S.; Nosanchuk, Joshua D.; Casadevall, Arturo.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 21, No. 2, 2006, p. 117-129.

Research output: Contribution to journalArticle

Dadachova, E, Moadel, T, Schweitzer, AD, Bryan, RA, Zhang, T, Mints, L, Revskaya, E, Huang, X, Ortiz, G, Nosanchuk, JS, Nosanchuk, JD & Casadevall, A 2006, 'Radiolabeled melanin-binding peptides are safe and effective in treatment of human pigmented melanoma in a mouse model of disease', Cancer Biotherapy and Radiopharmaceuticals, vol. 21, no. 2, pp. 117-129. https://doi.org/10.1089/cbr.2006.21.117
Dadachova, Ekaterina ; Moadel, Tiffany ; Schweitzer, Andrew D. ; Bryan, Ruth A. ; Zhang, Tong ; Mints, Lisa ; Revskaya, Ekaterina ; Huang, Xianchuan ; Ortiz, Geraldina ; Nosanchuk, Jerome S. ; Nosanchuk, Joshua D. ; Casadevall, Arturo. / Radiolabeled melanin-binding peptides are safe and effective in treatment of human pigmented melanoma in a mouse model of disease. In: Cancer Biotherapy and Radiopharmaceuticals. 2006 ; Vol. 21, No. 2. pp. 117-129.
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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 (188RE-HYNIC- 4B4) and a comprehensive safety evaluation of this treatment. 188RE-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 188RE-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 188RE-labeled decapeptide did not produce therapeutic gain. Repeated doses of 188RE-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 188RE-HYNIC-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 188RE-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.",
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