The positron emission tomography (PET) tracer 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl)-nortropane ((18)F-FECNT) is a highly specific
ligand for
dopamine transporter (DAT) that yields higher peak striatum-to-cerebellum ratios and offers more favorable kinetics than most (18)F-radiolabeled DAT
ligands currently available. The goal of this study is to validate the use of
(18)F-FECNT as a PET radiotracer to assess the degree of striatal
dopamine terminals
denervation and midbrain dopaminergic cell loss in
MPTP-treated parkinsonian monkeys. Three rhesus monkeys received weekly
injections of
MPTP (0.2-0.5 mg/kg) for 21 weeks, which resulted in the progressive development of a moderate level of
parkinsonism. We carried out
(18)F-FECNT PET at baseline (twice; 10 weeks apart) and at week 21 post-
MPTP injections. Postmortem stereological cell counts of dopaminergic neurons in the ventral midbrain, and intensity measurements of DAT and
tyrosine hydroxylase (TH) immunoreactivity in the striatum were performed and correlated with striatal and ventral midbrain PET data. Three additional monkeys were used as controls for midbrain dopaminergic cell counts, and striatal DAT or TH immunoreactivity measurements. The correlation and coefficient of variance between
(18)F-FECNT test-retest specific uptake ratios were 0.99 (R²) and 2.65%, respectively. The
(18)F-FECNT binding potential of the ventral midbrain and striatal regions was tightly correlated with postmortem stereological cell counts of nigral dopaminergic neurons (R²=0.91), and striatal DAT (R²=0.83) or TH (R²=0.88) immunoreactivity intensity measurements. These findings demonstrate that
(18)F-FECNT is a highly sensitive PET imaging
ligand to quantify both striatal
dopamine denervation and midbrain dopaminergic cell loss associated with
parkinsonism.