title: Metabolic and distribution studies with radiolabeled 5-fluorouracil.
abstract: 5-Fluorouracil (5-FU) is an effective anti-tumor drug, which has been used both as a single agent and in combination with other chemotherapeutic agents for the treatment of tumors such as breast and colorectal carcinoma. We synthesized 5-FU with trace amounts of 18F-5-FU and administered the compounds intravenously to 6 cancer patients. The patients were scanned at 2 hr intervals for 12 hrs and their urine collected whenever possible. We also injected 5-FU with the tracer 18F-5-FU, at pharmacological doses, into non-tumored rats, and sampled their bile and blood for 95 mins post-injection. For comparison, 2-14C-5-FU was injected into non-tumored rats and their bile and blood sampled at the same intervals. Minute quantities of rat bile and serum were analyzed chromatographically by high-performance TLC. 5-FU and two of its metabolites (FBAL and FUPA) were identified and quantified by this technique. Both percentage and absolute amounts of 5-FU in the bile follow comparative kinetic patterns. While the liver and the urinary bladder were clearly observable in all 16 patients, the detectability of the gall-bladder was correlated to the inverse of the alkaline phosphatase level in the blood. This work suggests that the diversity of the 5-FU metabolism in cancer patients may allow the use of 18F-5-FU as a probe for understanding those individual variabilities in clinical situations.
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001711:Biotransformation; D001943:Breast Neoplasms / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D005260:Female; D005461:Fluorine; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D011868:Radioisotopes; D051381:Rats; D014018:Tissue Distribution
chemical_list: D011868:Radioisotopes; D005461:Fluorine; D005472:Fluorouracil