Radiolabeled melanin-binding peptides are safe and effective in treatment of human pigmented melanoma in a mouse model of disease.
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.
Dadachova
Ekaterina
E
Department of Nuclear Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA. edadacho@aecom.yu.edu
Moadel
Tiffany
T
Schweitzer
Andrew D
AD
Bryan
Ruth A
RA
Zhang
Tong
T
Mints
Lisa
L
Revskaya
Ekaterina
E
Huang
Xianchuan
X
Ortiz
Geraldina
G
Nosanchuk
Jerome S
JS
Nosanchuk
Joshua D
JD
Casadevall
Arturo
A
D000818:Animals; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000627:therapeutic use; D000922:Immunotoxins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology; D008297:Male; D008543:Melanins / Q000737:chemistry / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009539:Nicotinic Acids / Q000737:chemistry / Q000627:therapeutic use; D010455:Peptides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
C120392:6-hydrazinopyridine-3-carboxylic acid; D006834:Hydrazines; D000922:Immunotoxins; D008543:Melanins; D009539:Nicotinic Acids; D010455:Peptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium