AT-211-METHYLENE BLUE FOR TARGETED RADIOTHERAPY OF DISSEMINATED MELANOMA - MICROSCOPIC ANALYSIS OF TUMOR VERSUS NORMAL TISSUE-DAMAGE

The present stage of our preclinical investigations of targeted radiot herapy for melanoma with 3,7-(dimethylamino)phenazathionium chloride [ methylene blue (MTB)] labelled with astatine-211 (At-211), an alpha-pa rticle emitter, concerns toxicity of the treatment, as well as macro- and microscopic evaluation of its efficacy. Fragments of two human mel anoma xenografts, pigmented HX118 and non-pigmented HX34 (used as a co ntrol), were implanted s.c. into nude mice subsequently treated with t wo doses of At-211-MTB injected i.v. Alterations in tumour growth rate were related to microscopic damage caused by At-211-MTB to the lesion s, as determined by light microscopy using histopathological technique s. At-211-MTB-dependent growth inhibition of pigmented melanoma occurr ed either instantly or as a gradual reduction in the tumour growth rat e. At a later stage, lesions that ceased to grow immediately consisted of quiescent, heavily pigmented tumour cells, as well as advanced fib rosis, and were extensively infiltrated by melanin-laden phagocytes. L arge, unresorbed and often calcified necrotic deposits characterised t he tumours responding gradually to the treatment. At-211-MTB remained non-toxic in normal organs. Only a relative number of small lymphocyte s in the groin lymph nodes in a minority of animals was temporarily re duced, most often in conjunction with the treatment of pigmented tumou rs. The data demonstrated a high therapeutic effectiveness of At-211-M TB towards pigmented melanoma at the expense of negligible injury to n ormal tissues, and revealed that the macroscopic determination of tumo ur growth rate often underestimated an efficacy of the applied treatme nt. Copyright (C) 1996 Published by Elsevier Science Ltd