title: Pharmacokinetics of the thymidine analog 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU) in tumor-bearing rats.
abstract: The thymidine analog 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU) is incorporated into DNA and is resistant to catabolism. We performed pharmacokinetic measurements with [(14)C]FMAU and PET studies with [(11)C]FMAU using rats bearing several different syngeneic tumors. Among normal tissues, FMAU uptake reflected relative cell turnover rates. Among tumors, the highest uptake occurred in a rapidly growing colon carcinoma, but was similarly low in both rapidly and slowly growing prostate tumors. FMAU was not catabolized and was rapidly incorporated into DNA by small intestine and colon tumors. Results indicate that FMAU may be useful for imaging tissue DNA synthesis, although tumor uptake was modest and not well correlated with growth rate among the models examined.
authors.affiliation: Department of Radiology, University of Southern California, Los Angeles, 90033, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Bading
authors.forename: Antranik H
authors.initials: AH
authors.lastname: Shahinian
authors.forename: Amy
authors.initials: A
authors.lastname: Vail
authors.forename: Pravin
authors.initials: P
authors.lastname: Bathija
authors.forename: G W
authors.initials: GW
authors.lastname: Koszalka
authors.forename: Robert T
authors.initials: RT
authors.lastname: Koda
authors.forename: Mian M
authors.initials: MM
authors.lastname: Alauddin
authors.forename: John D
authors.initials: JD
authors.lastname: Fissekis
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism; D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D013936:Thymidine / Q000031:analogs & derivatives / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D004273:DNA, Neoplasm; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C034935:clevudine; D013936:Thymidine