Thiourea as a melanoma targeting agent.
It has previously been shown that various thiourea derivatives are incorporated into nascent melanin, and a few of these substances, e.g. 2-thiouracil and its radioiodinated analogue, have been used for selective targeting of melanotic melanoma. Possible localization of thiourea itself in melanoma, however, has not been investigated so far. We have therefore performed the present autoradiographic and impulse counting study on the disposition of 14C-thiourea in mice transplanted with B16 melanoma. The results demonstrated a pronounced, but partly heterogeneous, uptake of radioactivity in the melanoma tissue, with the highest concentration 4 h after the injection. Four days after the administration of a single dose, the retention of label was still high in certain tumoral areas. The lung was the only normal tissue with a similarly high uptake of radioactivity. Additional experiments in vitro showed that the incorporation of thiourea into melanin was dose-dependent. The binding to performed melanin was found to be low, which strongly indicates that the incorporation of thiourea into melanin mainly is due to interaction with intermediates of the melanin synthetic pathway.
Mårs
U
U
Department of Pharmaceutical Biosciences, Biomedical Center, Uppsala University, Sweden.
Larsson
B S
BS
D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D007091:Image Processing, Computer-Assisted; D008543:Melanins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013890:Thiourea / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D008543:Melanins; D013890:Thiourea