Objective To investigate in-vivo changes in dopamine turnover in Parkinson's disease (PD) with COMT val158met functional polymorphism using 18F-dopa positron emission tomography (PET).
Methods Twenty patients with PD (10 with val/val, and 10 with met/met homozygosity) underwent 18F-dopa PET scans using a prolonged imaging protocol of upto 3.5 h. The first dynamic scan was acquired 0–90 min (the early scan) post intravenous radioligand administration, with the second scan (late scan) acquired at 150–210 min. Patients were matched for age, sex, verbal IQ, disease duration and severity. Data were analysed using an a priori regions of interest approach, and calculated 18F-dopa influx constant (Ki) were compared using Analysis of Variance for frontal and striatal regions.
Results The Ki values were significantly reduced in both frontal and striatal regions of interest in both groups in the late scan compared to the early scan. Furthermore, during the late scan, met/met patients had significantly higher Ki values compared to their val/val counterparts in the anterior cingulated, superior frontal and mid-frontal, while values were similar between the two groups during the early scan.
Discussion This is the first in vivo study in Parkinsonian subjects using a prolonged 18F-dopa PET scanning protocol to detect differences in dopamine influx constant in the functional COMT val158met polymorphism. Our results suggest that a higher Ki constant, indicative of a higher presynaptic dopamine level in the frontal regions of met homozygotes, supports clinical data on the distinct phenotypic differences as found in other studies.
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