TY - JOUR
T1 - Radiolabeled melanin-binding peptides are safe and effective in treatment of human pigmented melanoma in a mouse model of disease
AU - Dadachova, Ekaterina
AU - Moadel, Tiffany
AU - Schweitzer, Andrew D.
AU - Bryan, Ruth A.
AU - Zhang, Tong
AU - Mints, Lisa
AU - Revskaya, Ekaterina
AU - Huang, Xianchuan
AU - Ortiz, Geraldina
AU - Nosanchuk, Jerome S.
AU - Nosanchuk, Joshua D.
AU - Casadevall, Arturo
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - 188-Rhenium
KW - Melanin
KW - Melanin-binding peptide
KW - Melanoma
KW - Nude mice
KW - Radiolabeled peptides
KW - Therapy
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U2 - 10.1089/cbr.2006.21.117
DO - 10.1089/cbr.2006.21.117
M3 - Article
C2 - 16706632
AN - SCOPUS:33744827431
SN - 1084-9785
VL - 21
SP - 117
EP - 129
JO - Cancer Biotherapy and Radiopharmaceuticals
JF - Cancer Biotherapy and Radiopharmaceuticals
IS - 2
ER -