Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: a comparative animal study.
The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas.
Brix
G
G
Research Program Radiological Diagnostics and Therapy, German Cancer Research Center (DKFZ), Heidelberg, Germany. G.Brix@dkfz-heidelberg.de
Bellemann
M E
ME
Haberkorn
U
U
Gerlach
L
L
Lorenz
W J
WJ
D000818:Animals; D005462:Fluorine Radioisotopes; D005472:Fluorouracil / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism; D051381:Rats; D011912:Rats, Inbred ACI; D011915:Rats, Inbred BUF; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D005472:Fluorouracil