Radioactive derivatives of 2-methyl-1, 4-naphthoquinol bis (diphosphate salt) as anti-cancer drugs with high LET radiations.
From the results of the alpha-particle track autoradiography, the alkaline phosphatase studies, the biodistribution investigations and the therapeutic experiments with the transplanted Franks and Hemmings (1978) adenocarcinoma of the rectum in mice, an important finding is the striking selectivity of the uptake of the compound 6-211 At-astato-2-methyl-1, 4-naphthoquinol bis (diphosphate salt), after intraperitoneal injection into the tumour cell nuclei and in many cases into the nuclei of tumour stem cells, together with negligible uptake into normal colon and narrow. The compound, 6-211 At-astato-2-methyl-1, 4-naphthoquinol bis (diphosphate salt) has been found to cure about two-thirds of the transplanted adenocarcinoma of the rectum in mice after a single intra-peritoneal injection of 3-4 microCi. This approach can be regarded as a form of metabolically-directed drug targetting on to a tumour product which is an enzyme, an alkaline phosphatase isozyme, present in the cells of some tumours. The compound is being studied further from the point of view of possible human therapeutic applications.
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D001246:Astatine / Q000627:therapeutic use; D001966:Bromine / Q000627:therapeutic use; D004735:Energy Transfer; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000201:enzymology / Q000532:radiotherapy*; D010766:Phosphorylation; D011868:Radioisotopes / Q000627:therapeutic use*; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use
D011868:Radioisotopes; D014812:Vitamin K; D000469:Alkaline Phosphatase; D001966:Bromine; C023885:menadiol; D001246:Astatine