Distribution kinetics of 18F-DOPA in weaver mutant mice.
Distribution kinetics of 18F-fluoro-dihydroxy phenylalanine (18F-DOPA) were studied with high-resolution micro-positron emission tomography (microPET) imaging and conventional methods in control wild-type mice, heterozygous weaver mutant mice, and homozygous weaver mutant mice. 18F-DOPA uptake was significantly increased in the CNS within 60 min in all the genotypes examined. Homozygous weaver mutant mice exhibited significantly reduced 18F-DOPA uptake in the region of interest (striatum) as compared to heterozygous weaver mutant mice and control wild-type mice. 18F-DOPA was de-localized in the kidneys of homozygous weaver mutant mice. The radioactivity was localized primarily in the liver and kidneys within 2 h and in the urinary bladder within 4 h. After 8 h, it could be detected neither by conventional nor by microPET imaging. Distribution kinetics of 18F-DOPA with microPET imaging correlated and confirmed the conventional observations. These data are interpreted to suggest that microPET imaging may provide an efficient, noninvasive, cost-effective procedure to study distribution kinetics of PET radiopharmaceuticals in rare genetically altered animals. Furthermore, this unique and noninvasive approach may expedite quality control and drug development for human applications.
Center of Excellence in Neuroscience, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58203, USA.
Sushil K
SK
Sharma
Manuchair
M
Ebadi
D000818:Animals; D002490:Central Nervous System / Q000033:anatomy & histology / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000737:chemistry / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D049268:Positron-Emission Tomography
D005462:Fluorine Radioisotopes; D004295:Dihydroxyphenylalanine