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

Abstract

6‐[¹⁸F]Fluoro‐L‐DOPA (FDOPA) cerebral kinetics and metabolism were correlated in normal primates (Macaca nemestrina) and primates with 1‐methyl‐4‐phenyl‐l,2,3,6‐tetrahydropyridine (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‐[¹⁸F]fluorodopamine (FDA) radioactivity in normal striatum (k₄ = 0.005/min, turnover half‐time ≥ 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[¹⁸F]fluorohomovanillic (FHVA) and 6‐[¹⁸F]fluoro‐3, 4‐dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3‐0‐methyl‐6‐[¹⁸F]fluoro‐L‐DOPA (3‐OMFD) of peripheral origin. The (FHVA + FDOPAc)/FDA ratio was 1:2 in normal putamen and ≥6:1 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‐induccd Parkinsonism).