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Dopamine Transporter Imaging with Fluorine-18-FPCIT and PET

Departments of Neurology and Research, North Shore University Hospital, Manhasset
New York University School of Medicine, New York, New York
Department of Psychiatry, McLean Hospital, Belmont
Harvard Medical School, Boston, Massachusetts

Correspondence: For correspondence or reprints contact: David Eidelberg, MD, Department of Neurology, North Shore University Hospital, 350 Community Drive, Manhasset, New York, 11030.

ABSTRACT

Fluorinated N-3-fluoropropyl-2- ß-carboxymethoxy-3-ß-(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 Q(k'₂= 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.

Key Words: fluorine-18-fluorinated N-3-fluoropropyl-2-ß-carboxymethoxy-3-ß-(4-iodophenyl) nortropane • PET • dopamine transporter • Parkinson's disease • aging effect

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