Fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (FPCIT) has been synthesized as a dopamine transporter ligand for PET studies. We evaluated the regional brain uptake and the plasma metabolism of [18F]-FPCIT.
Methods: PET studies were conducted on 7 normal subjects and on 10 patients with Parkinson's disease. After the [18F]-FPCIT injection (4.4+/-1.8 mCi), dynamic scans were acquired over 100 min. Plasma metabolite analysis was performed using high-performance liquid chromatography (HPLC).
Results: Plasma HPLC revealed two peaks corresponding to unmetabolized [18F]-FPCIT and a polar metabolite. The fraction of the parent compound decreased rapidly to 25% at 25 min. Fluorine-18-FPCIT showed a striatum-to-occipital ratio (SOR) of 3.5 at 90 min postinjection. The ratio of striatal-to-occipital distribution volume (DVR) was calculated directly by using a mean tissue-to-plasma efflux constant for occipital cortex obtained in 10 subjects (ki=0.037 min(-1)). DVR measures determined with and without plasma input function were correlated (r=0.98, p < 0.0001). In normal subjects, a significant age-related decline of DVR was observed both for caudate and putamen, corresponding to a 7.7% and 6.4% decline per decade, respectively (r > 0.85, p < 0.01). Both DVR and SOR correctly classified early-stage Parkinson's disease patients with comparable accuracy (p < 0.0001). Age-corrected DVR values correlated negatively with the Uniform Parkinson's Disease Rating Scale composite motor ratings (r=0.66, p < 0.05).
Conclusion: The tracer characteristics are compatible with a high-affinity, reversible ligand. FPCIT/PET demonstrated age-related decline in dopamine transporter binding in normal subjects as well as significant reductions in patients with idiopathic Parkinson's disease, which correlates with the disease severity.