211At-methylene blue in targeted radiotherapy of disseminated melanoma.
Targeted radiotherapy with 211At-methylene blue (211At-MTB) is a systemic treatment selectively directed at melanoma due to a high affinity of MTB to melanin synthesized in the tumor cells. Since MTB forms a strong complex with melanin, it is an effective carrier for a number of radioisotopes to be addressed to the tumor deposits of any size including individually dispersed melanoma cells. Thus, appropriately radiolabeled MTB can be used for either diagnosis or therapy of the neoplasm. As predicted and found in animal experiments, 211At-MTB is most effective therapeutically. Histopathological investigations showed that the highly pigmented 211At-MTB-treated tumors were characterized initially by perivascular oedema and hydropic degeneration of tumor cells followed by gradual development of extensive areas of coagulative necrosis. The necrotic tumor areas contained microvessels occluded by thrombi and tended to undergo microfocal calcification. Although melanoma-bearing animals successfully treated with 211At-MTB did not reveal any adverse effects of the therapy, detailed toxicological studies were undertaken. No serious macro- or microscopic lesions were observed in normal organs of 211At-MTB treated mice. Only the relative number of small lymphocytes in the groin lymph nodes in a minority of animals was variably reduced, most often in conjunction with the treatment of highly, but not poorly, pigmented tumors.
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Department of Molecular Pathology, University College London Medical School, UK.
Michalowski
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Rösch
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D000818:Animals; D001246:Astatine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004337:Drug Carriers; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000532:radiotherapy*; D008751:Methylene Blue; D051379:Mice
D004337:Drug Carriers; D008751:Methylene Blue; D001246:Astatine