Boron Neutron Capture Therapy for Malignant Melanoma: An Experimental Approach

Previous studies have shown that some thioamides, e.g., thiouracil, are incorporated as false precursors into melanin during its synthesis. If boronated analogs of the thioamides share this property, the melanin of melanotic melanomas offers a possibility for specific tumoural uptake and retention of boron as a basis for neutron capture therapy. We report on the synthesis of boronated 1H‐1,2,4‐triazole‐3‐thiol (B‐TZT), boronated 5‐carboxy‐2‐thiouracil (B‐CTU), and boronated 5‐diethylaminomethyl‐2‐thiouracil (B‐DEAMTU) and the localization of these substances in melanotic melanomas transplanted to mice. The distribution in the mice was studied by boron neutron capture radiography. B‐TZT and B‐CTU showed the highest tumour:normal tissue concentration ratios, with tumour:liver ratios of about 4 and tumour:muscle ratios of about 14; B‐DEAMTU showed corresponding ratios of 1.4 and 5, respectively. The absolute concentration of boron in the tumours, however, was more than three times higher in the mice injected with B‐TZT, compared with B‐CTU. The results suggest that B‐TZT may be the most promising compound of the three tested with regard to possible therapy of melanotic melanomas.