6-( sup 18 F)fluoro-L-dopa probes dopamine turnover rates in central dopaminergic structures

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Journal of Neuroscience Research; (USA)

DOI:https://doi.org/10.1002/jnr.490270408· OSTI ID:5683710

Barrio, J R; Huang, S C; Melega, W P; Yu, D C; Hoffman, J M; Schneider, J S; Satyamurthy, N; Mazziotta, J C; Phelps, M E ^[1]

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1. UCLA School of Medicine (USA)

6-({sup 18}F)Fluoro-L-DOPA (FDOPA) cerebral kinetics and metabolism were correlated in normal primates (Macaca nemestrina) and primates with 1-methyl-4-phenyl-1,2,3,6-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-({sup 18}F)fluorodopamine (FDA) radioactivity in normal striatum (k4 = 0.005/min, turnover half-time greater than or equal to 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({sup 18}F)fluorohomovanillic (FHVA) and 6-({sup 18}F)fluoro-3, 4-dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3-0-methyl-6-({sup 18}F)fluoro-L-DOPA (3-OMFD) of peripheral origin. The (FHVA + FDOPAC)/FDA ratio was 1:2 in normal putamen and greater than or equal to 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-induced Parkinsonism).

• OSTI ID: 5683710
• Journal Information: Journal of Neuroscience Research; (USA), Journal Name: Journal of Neuroscience Research; (USA) Vol. 27:4; ISSN JNRED; ISSN 0360-4012
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
AMINO ACIDS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BLOOD-BRAIN BARRIER
BODY
BRAIN
CARBOXYLIC ACIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
COMPUTERIZED TOMOGRAPHY
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DISEASES
DOPA
DOPAMINE
DRUGS
EMISSION COMPUTED TOMOGRAPHY
FLUORINE 18
FLUORINE ISOTOPES
HOURS LIVING RADIOISOTOPES
HYDROXY ACIDS
HYDROXY COMPOUNDS
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
METABOLISM
MONKEYS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
RADIOISOTOPES
SYMPATHOMIMETICS
TOMOGRAPHY
TRACER TECHNIQUES
VERTEBRATES