Melanin-affinic thioureas as selective melanoma seekers

Abstract

2-Thiouracil and some related thioureas are receiving growing interest as selective melanoma seekers. They are incorporated into growing melanin, apparently due to covalent binding to dopaquinone, and the adduct is gradually trapped in the melanin polymer during its formation. To be clinically useful in melanoma scanning, thiouracil has been radioiodinated, and 5-iodo-2-thiouracil (ITU) was found to be localized in melanotic melanoma as selectively as thiouracil. Clinical trials with ITU, for the detection of malignant melanoma, are in progress, and the results so far are promising. Treatment with [35S]thiouracil has been performed on melanoma-bearing mice. The radiodoses needed for cure, however, were very high, which makes clinical application hazardous. Boron neutron capture therapy, on the other hand, might be a better approach. The technique is based on the irradiation of tumours with slow neutrons from an external source after the accumulation of boron in tumour tissue and clearance from normal tissues. Boron-10 undergoes instantaneous nuclear fission through the reaction 10B(n,alpha)7Li, and the emitted particles are efficient in cell killing. Boronated thioureas have been synthesized in various laboratories, and data from experiments on melanoma-bearing mice indicate that some of these compounds accumulate in the tumours in concentrations necessary for successful treatment.