6-[18F]Fluoro-L-DOPA probes dopamine turnover rates in central dopaminergic structures

✍ Scribed by Dr. J. R. Barrio; S. C. Huang; W. P. Melega; D. C. Yu; J. M. Hoffman; J. S. Schneider; N. Satyamurthy; J. C. Mazziotta; M. E. Phelps

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 664 KB
• Volume: 27
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490270408

✦ Synopsis

6-['8F

]Fluor~-L-DOPA (FDOPA) cerebral kinetics and metabolism were correlated in normal primates (Mucacu nemestrina) and primates with l-methyl-4phenyl-l,2,3,64etrahydropyridine (MPTP) induced unilateral Parkinsonism. Application of a tracer kinetic model to positron emission tomography (PET) data indicated that the model allows reliable estimation of FDOPA blood brain barrier transport, decarboxylation and release of stored 6-[1SF]fluorodopamine (FDA) radioactivity in normal striatum (k4 = O.OOS/min, turnover half-time 2 2 hr), in agreement with biochemical data. PET scans of MPTP treated monkeys revealed 40-50% reduction in total striatal activity in comparison with pre-MPTP scans. Monkey brain biochemical analysis revealed that the reduction in activity was mainly due to a decrease in FDA and its metabolites, 6[1SF]fluorohomovanillic (FHVA) and 6-['SF]fluoro-3, 4-dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3-O-methyl-6-[1sF]fluoro-L-DOPA (3-OMFD) of peripheral origin. The (FHVA + FDOPAC)/FDA ratio was 1:2 in normal putamen and 16:l in the lesioned putamen, indicative of a dramatic increase in turnover of FDA. Both kinetic and biochemical data indicate that FDOPA labels a slow turnover rate pool of dopamine in rat and primate brain. This turnover rate for stored dopamine (DA) is accelerated with dopaminergic cell losses (e.g., MPTP-induced Parkinsonism).