Uptake of 6‐[18F]fluoro‐L‐dopa and [18F]CFT reflect nigral neuronal loss in a rat model of Parkinson's disease
Abstract
In order to characterize the sensitivity of an analog of levodopa and a dopamine transporter ligand to detect defects in nigrostriatal function, the uptake of [18F]FDOPA and [18F]CFT was studied ex vivo in a rat model of Parkinson's disease. The brains of these rats were unilaterally lesioned with an intranigral injection of 6‐hydroxydopamine. The lesioned animals were divided into three groups subject to their behavior after pharmacological challenges. Circling behavior was recorded after amphetamine, apomorphine, and L‐DOPA challenge in order to predict lesion size. The spatial distribution of radioactivity after [18F]FDOPA or [18F]CFT injection in brain sections was determined with digital autoradiography. Regions of interest were left/right striatum, left/right substantia nigra, and cerebellum. The degree of unilateral lesion for each animal was confirmed by counting of nigral tyrosine hydroxylase‐positive cell bodies. With both tracers the uptake in the lesioned side was lower than in the intact side in the striatum and in the substantia nigra. In conclusion, both tracers clearly demonstrated nigrostriatal dopaminergic hypofunction and correlated with the number of nigral dopaminergic neurons. However, [18F]FDOPA showed a much higher unspecific uptake of radioactivity, due to extensive metabolism; therefore, this tracer was less sensitive than the transporter tracer [18F]CFT to detect these defects. Synapse 51:119–127, 2004.Keywords
Funding Information
- Paivikki and Sakari Sohlberg Foundation
- Turku University Hospital (EVO)
This publication has 29 references indexed in Scilit:
- Comparison between the decrease of dopamine transporter and that ofL-DOPA uptake for detection of early to advanced stage of Parkinson's disease in animal modelsSynapse, 1999
- Time course of changes in striatal dopamine transporters and D2 receptors with specific iodinated markers in a rat model of Parkinson's diseaseSynapse, 1999
- Human positron emission tomographic [18F]Fluorodopa studies correlate with dopamine cell counts and levelsAnnals of Neurology, 1993
- The Effect of Catechol-O-Methyl Transferase Inhibition by Entacapone on the Pharmacokinetics and Metabolism of Levodopa in Healthy VolunteersClinical Neuropharmacology, 1993
- Administration of the new COMT inhibitor OR‐611 increases striatal uptake of fluorodopaMovement Disorders, 1993
- Regioselective radiofluorodestannylation with [18F]F2 and [18F]CH3COOF: A high yield synthesis of 6-[18F]fluoro-l-dopaInternational Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes, 1992
- Striatal function in normal aging: Implications for Parkinson's diseaseAnnals of Neurology, 1990
- Cerebral Metabolism of 6–[18F]Fluoro‐l‐3,4‐Dihydroxyphenylalanine in the PrimateJournal of Neurochemistry, 1987
- The Metabolism of [18F]6‐Fluoro‐l‐3,4‐Dihydroxyphenylalanine in the Hooded RatJournal of Neurochemistry, 1987
- Compounds Affecting the Central Nervous System. 4. 3.beta.-Phenyltropane-2-carboxylic Esters and AnalogsJournal of Medicinal Chemistry, 1973