Preliminary observations of malignant melanoma therapy using radiolabeled alpha-methyltyrosine

Abstract

A strategy for cancer therapy using astatine-211-labeled alpha-methyltyrosine (²¹¹At-AMT) was studied in cultured B16 melanoma cells and compared to the radiotoxicity of iodine-125-labeled iododeoxyuridine (¹²⁵IUdR), a thymidine analogue. Both ¹²⁵I and ²¹¹ At deliver lethal doses of irradiation to melanoma cells when administered as ¹²⁵IUdR and ²¹¹At-AMT. The alpha decay of astatine-211 is more effective however, needing only a fraction of the cellular radioactivity of ¹²⁵IUdR to effect comparable clonogenic survival. Compared with ¹²⁵IUdR, ¹²⁵I-AMT is not cytotoxic because the range of the low energy electrons released does not interact with DNA. Uptake of radiolabeled AMT by melanotic cells is enhanced by theophylline. This preliminary evidence suggests that ²¹¹At-labeled melanin precursors may be exquisitely cytotoxic to B16 melanoma cells.