Sixteen subjects with de novo Parkinson's disease (PD) underwent three 6-[18F]fluoro-L-dopa (Fdopa) positron emission tomography (PET) scans during a follow-up time of 5 years (mean +/- SD 5.5 +/- 0.4 years) to study the progression of striatal dopaminergic hypofunction. Throughout the study, the smallest Fdopa uptake values were found in the dorso-caudal part of the putamen contralateral to the side with dominant motor symptoms. The rate of decline in Fdopa uptake in the contralateral putamen was faster in the beginning of the disease and slowed down as the disease progressed. The annual decline in Fdopa influx constant (Ki, unit x 10(-3) min(-1)) was on average 0.5 during the first 2 years and 0.2 during the subsequent 3 years (P = 0.002) in the contralateral putamen. In caudate, the rate of decline in Fdopa values was slower than in the putamen and did not change significantly during the follow-up time, annual decline in the contralateral caudate being 0.1 between baseline and 2 years and 0.3 between 2 and 5 years (P = 0.4). These results suggest that progression of putaminal dopaminergic hypofuncion in PD follows a nonlinear pattern at least in the contralateral side being faster in the beginning of the disease.

6-18 F-fluoro-L-dopa ( 18 F-FDOPA) is widely used to investigate dopaminergic hypofunction, for instance, in Parkinson disease (PD). Conventionally, a 90-min scan with either a graphical or a metabolite-purified plasma input approach has been used for quantification. In the clinical setting, to increase compliance, especially in patients with more advanced disease, and to increase the efficacy of tracer and scanner time use, a shorter acquisition and a simple quantitative analysis are desirable. Taking into account the asymmetry of clinical symptoms and the uneven distribution of striatal dopaminergic hypofunction may also improve the use of 18 F-FDOPA PET in early disease detection. Therefore, we compared subregional striatal 18 F-FDOPA PET data from a large group of nonmedicated patients with early PD and a set of healthy elderly volunteers to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. Methods: A total of 89 nonmedicated patients with early PD and 21 healthy volunteers were studied with 18 F-FDOPA PET, and both a region-to-reference (striatal-to-occipital) ratio (SOR) calculated from 75 to 90 min after injection and a graphical analysis of data calculated from 15 to 90 min after 18 F-FDOPA injection (yielding the influx constant [K i ref ]) were used. Results: Both SOR and K i ref values in the PD patients were lowest, relative to those in the healthy controls, in the posterior putamen contralateral to the side with predominant clinical symptoms. The contralateral posterior putamen showed the largest areas under the receiver operating characteristic (ROC) curve-0.994 for SOR and 0.998 for K i ref -indicating excellent separation of the PD and control groups. The caudate nucleus and the ventral striatum were less impressive in this respect. Conclusion: A single 15-min scan 75 min after tracer injection seems to be sufficient for separating patients with PD from healthy controls in a clinical research environment. This method represents a powerful and economical alternative for research on the disease mechanism and differential diagnosis.