Preliminary observations of malignant melanoma therapy using radiolabeled alpha-methyltyrosine

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.