Dopaminergic Activity and Cognitive Function in de novo Parkinson Disease patients: an 18F-DOPA PET/CT study

Background Even at the early stage of Parkinson’s Disease (PD) nuclear medicine‐ techniques, such as 123 I‐FP‐CIT SPECT and 123 I ‐MIBG scintigraphy, may reveal pathological findings, showing striatum and cardiac reduced uptake, respectively. This information about nigro‐striatal and sympathetic cardiac neuronal loss may contribute to the early diagnosis of PD and provide relevant elements for differential diagnosis between PD and other parkinsonian syndrome. The main limitation to investigate these different neuronal systems, is related to the need of two scans, with two tracers and double radiation exposure for patients. 18 F‐DOPA is a dopamine precursor able to evaluate synthetic and storage capacity of dopamine in pre‐synaptic terminals. This PET radiopharmaceutical is a sensitive bio‐marker to assess nigro‐striatal dysfunction and its diagnostic accuracy is comparable to those of 123 I‐FP‐CIT. However, 18 F‐DOPA has never been validate so far as a biomarker of cardiac sympathetic denervation, despite its cardiac uptake. Our aim is evaluating the association between cardiac and striatal 18 F‐DOPA uptake in de novo PD, in order to test whether it may be further evaluated as a biomarker of cardiac neuronal loss. Methods Sixteen patients with de novo PD were included in this study. Patients with history of coronary artery disease and diabetes mellitus were excluded from the study. The patients were given carbidopa (2,5 mg/Kg) orally, and after 60 min, received 185 MBq of 18 F‐DOPA. PET/CT was acquired 90 min after the injection. Cardiac 18 F‐DOPA‐PET/CT was acquired at the end of brain scan. Automatic segmentation and semiquantification of 18 F‐DOPA striatal uptake was asses using basal ganglia matching tools package. Regions of interest were drawn over the heart and mediastinum. The ratio between the uptake in the left ventricle and mediastinum (H/M ratio) was recorded for each scan. Results Both in case of putamen (r=0.75, p=0.0009) and caudate (r=0.57, p=0.02) , a significant correlation between the more affected site of striatal uptake and H/M ratio was found. Direct correlation between striatal uptake and H/M ratio was confirmed also in the controlateral site (putamen: r=0.63, p= 0.0096; caudate: r=0.54, p=0.03). No significant inverse correlation was found between UPDRS III and H/M ratio (r=‐ 0.3630, p= 0.16). Conclusion These findings support the hypothesis that cardiac 18 F‐ DOPA uptake may be used as a biomarker of cardiac neuronal loss. If they were confirmed, it will be feasible to image striatal and cardiac pre‐synaptic monoaminergic function with a single radiopharmaceutical, dual acquisition, and PET/CT resolution, thus sparing radiation exposure and costs.