[AT-211]LMETHYLENE BLUE FOR TARGETED RADIOTHERAPY OF HUMAN-MELANOMA XENOGRAFTS - DOSE FRACTIONATION IN THE TREATMENT OF CUTANEOUS TUMORS

3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] la belled with alpha-particle emitter astatine-211 (At-211) selectively a ccumulates in melanoma cells due to an exceptionally high affinity of MTB to melanin, and proves to be a very effective agent in targeted ra diotherapy for pigmented human melanoma grown in mice. This study aime d at a selection of the most advantageous [At-211]MTB dose fractionati on leading to irreversible regression of the treated lesions. Nude mic e bearing subcutaneous human melanoma xenografts of either highly pigm ented HX118 or poorly pigmented HX34 human melanoma were treated with [At-211]MTB administered intravenously. The treatment was performed us ing three different schedules of [At-211]MTB fractionation: a single l arge dose, five fractions delivered sequentially every 48 h and two to five fractions given with a mean frequency of one per week. The effec tiveness of [At-211]MTB treatment was assessed by determination of the growth rate of cutaneous tumours and length of time between tumour im plantation and killing of moribund mice. [At-211]MTB applied with a me an frequency of one fraction per week appeared to be the most efficien t treatment for highly pigmented HX118 melanomas. Its effectiveness wa s dependent on [At-211]MTB activity used per fraction and the size of the cutaneous tumours at the beginning of the treatment. A total dose of [At-211]MTB Seemed of less importance. An irreversible regression o f the lesions was achieved. Poorly pigmented cutaneous melanoma xenogr afts were affected most significantly by [At-211]MTB applied as five f ractions given every 48 h. The treatment caused a temporary inhibition of tumour growth after which the lesions regained the control growth rate. These and previous results suggest that [At-211]MTB could succes sfully control the growth of already formed lesions of pigmented melan oma, as well as prevent metastatic spread of the tumour, provided an a ppropriate fractionation regime of the radiolabelled compound is emplo yed. Copyright (C) 1996 Elsevier Science Ltd.