Pharmacokinetics of the thymidine analog 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU) in tumor-bearing rats.
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.
Bading
James R
JR
Department of Radiology, University of Southern California, Los Angeles, 90033, USA.
Shahinian
Antranik H
AH
Vail
Amy
A
Bathija
Pravin
P
Koszalka
G W
GW
Koda
Robert T
RT
Alauddin
Mian M
MM
Fissekis
John D
JD
Conti
Peter S
PS
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
D002250:Carbon Radioisotopes; D004273:DNA, Neoplasm; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C034935:clevudine; D013936:Thymidine