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 [(18)F]FDOPA and [(18)F]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 [(18)F]FDOPA or [(18)F]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, [(18)F]FDOPA showed a much higher unspecific uptake of radioactivity, due to extensive metabolism; therefore, this tracer was less sensitive than the transporter tracer [(18)F]CFT to detect these defects.