DOPAMINE TRANSPORTER IMAGING WITH FLUORINE-18-FPCIT AND PET

Fluorinated propyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortrop ane (FPCIT) has been synthesized as a dopamine transporter ligand for PET studies. We evaluated the regional brain uptake and the plasma met abolism of [F-18]-FPCIT. Methods: PET studies were conducted on 7 norm al subjects and on 10 patients with Parkinson's disease. After the [F- 18]-FPCIT injection (4.4 +/- 1.8 mCi), dynamic scans were acquired ove r 100 min. Plasma metabolite analysis was performed using high-perform ance liquid chromatography (HPLC), Results: Plasma HPLC revealed two p eaks corresponding to unmetabolized [F-18]-FPCIT and a polar metabolit e. 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 distrib ution volume (DVR) was calculated directly by using a mean tissue-to-p lasma efflux constant for occipital cortex obtained in 10 subjects (k( 2)(') = 0.037 min(-1)). DVR measures determined with and without plasm a input function were correlated (r = 0.98, p < 0.0001). In normal sub jects, a significant age-related decline of DVR was observed both for caudate and putamen, corresponding to a 7.7% and 6.4% decline per deca de, respectively (r > 0.85, p < 0.01). Both DVR and SOR correctly clas sified early-stage Parkinson's disease patients with comparable accura cy (p < 0.0001). Age-corrected DVR values correlated negatively with t he Uniform Parkinson's Disease Rating Scale composite motor ratings (r = 0.66, p < 0.05), Conclusion: The tracer characteristics are compati ble with a high-affinity, reversible ligand. FPCIT/PET demonstrated ag e-related decline in dopamine transporter binding in normal subjects a s well as significant reductions in patients with idiopathic Parkinson 's disease, which correlates with the disease severity.