The present stage of our preclinical investigations of
targeted radiotherapy for
melanoma with 3,7-(dimethylamino)phenazathionium
chloride [methylene blue (MTB)] labelled with
astatine-211 (211At), an alpha-particle emitter, concerns toxicity of the treatment, as well as macro- and microscopic evaluation of its efficacy. Fragments of two human
melanoma xenografts, pigmented HX118 and non-pigmented HX34 (used as a control), were implanted s.c. into nude mice subsequently treated with two doses of 211At-MTB injected i.v. Alterations in tumour growth rate were related to microscopic damage caused by 211At-MTB to the lesions, as determined by light microscopy using histopathological techniques. 211At-MTB-dependent growth inhibition of pigmented
melanoma occurred either instantly or as a gradual reduction in the tumour growth rate. At a later stage, lesions that ceased to grow immediately consisted of quiescent, heavily pigmented tumour cells, as well as advanced
fibrosis, and were extensively infiltrated by
melanin-laden phagocytes. Large, unresorbed and often calcified necrotic deposits characterised the tumours responding gradually to the treatment. 211At-MTB remained non-toxic in normal organs. Only a relative number of small lymphocytes in the groin lymph nodes in a minority of animals was temporarily reduced, most often in conjunction with the treatment of pigmented tumours. The data demonstrated a high therapeutic effectiveness of 211At-MTB towards pigmented
melanoma at the expense of negligible injury to normal tissues, and revealed that the macroscopic determination of tumour growth rate often underestimated an efficacy of the applied treatment.