21IAt-Methylene Blue for Targeted Radiotherapy of Human Melanoma Xenografts: Treatment of Micrometastases1

Treatment of micrometastases of HX34 human melanoma grown as xenografts in nude mice represents an advanced stage of preclinical investigations concerning targeted radiotherapy of this neoplasm using 3,7-(dimethylamino)phenazathionium chloride (méthylà ̈ne blue (MTB) labeled with astatine-211 (2"At) (a-particle emitter). The therapeutic effectiveness of 2"At-MTB administered i.v. was determined by a lung colony assay combined with a search for métastases to organs other than the lungs. A single dose of 2"At-MTB lowered the HX34 cell surviving fraction in lungs to below 10% almost independently of the time interval between cell inoculation and radioisotope injection and of "At M l H radioactivity within its investigated range. Radiation dose and the time of its administration did, however, influence the size of lung colonies. In contrast, the efficacy of ;" At-M l B treatment as assessed by both sur viving fraction and colony size was significantly dependent on a number of HX34 cells inoculated initially into mice. These results are explained by a short range of a-particles emitted by '"At and a mechanism of growth of lung colonies from tumor cells circulating with blood and blocking lung capillaries. Métastasesin organs other than lungs and characteristic of control animals were not found in mice treated with 2"At-MTB. The high therapeutic efficacy achieved proved that 2"AtMTB is a very efficient scavenger of single melanoma cells distributed through blood and micrometastases with sizes below the limit of clinical detection.