Abstract
2480
Introduction: In today’s diagnosis of Parkinson’s disease (PD), an increasing number of clinical practices and researches have focused on non-motor symptoms (NMSs) beyond the traditional motor disorders. Gastrointestinal (GI) symptoms, one of the most common NMSs, can either occur in the prodromal stage of PD or throughout the whole disease period. Accumulating evidence suggests that PD may arise from the GI systems since the major pathogenic protein α-synuclein can aggregate and transmit from gut to the brain. However, few study has probed to the concurrent changes of human dopaminergic neurons both in the brain and GI systems. With the advantage of the total-body PET/CT scanner, we performed a real-time, dynamic 11C-CFT PET/CT imaging and investigated the relationships of the dopamine transporter (DAT) distribution across the “brain-GI” axis.
Methods: Dynamic total-body PET/CT (uEXPLORER, UIH) scans were performed on 10 subjects (4 PD patients and 6 healthy volunteers as reference). With a bedside bolus injection of 438.7±78.3 MBq 11C-CFT, PET acquisition was launched synchronously up to 75 min. Volumes of interest (VOIs) of the GI organs (pancreas, stomach, and duodenum) and brain nuclei (caudate, putamen, pallidum, and substantia nigra) were delineated on PET images to generate time-activity curves (TAC) and correlation analyses. Spearman’s correlation based on SPS Statistics was used for statistical analysis. P-value < 0.05 was considered statistically significant.
Results: According to the dynamic changing tendency of the mean standard uptake value (SUVmean) (g/mL) from the 11C-CFT tracer, we chose the early phase (0.8-3min) and late phase (60-75min) from the entire TAC to analyze. In the early phase of the healthy volunteers, the pancreas DAT distribution was positively correlated with the tracer uptakes in caudate and pallidum (both r=0.886, p=0.019); and the duodenum DAT distribution was positively correlated with the putamen and substantial nigra (both r=0.829, p=0.042). In the late phase of the healthy volunteers, positive correlation relationships were uniformly determined between the DAT distributions of pancreas and caudate (r=0.829, p=0.042), putamen (r=0.943, p=0.005), pallidum (r=0.886, p=0.019), as well as substantial nigra (r=1.000, p=0.000). Besides, the early phase of pancreas DAT distribution in healthy volunteers was also found highly correlated with the late phase tracer uptakes of putamen (r=0.829, p=0.042), pallidum (r=1.000, p=0.000), and substantial nigra (r=0.886, p=0.019). On the other hand, no correlation relationships resulted in either the early or the late phase of DAT distributions in PD patients between the interested GI organs and brain nuclei.
Conclusions: The application of dynamic 11C-CFT total-body PET/CT enabled a precise evaluation of DAT distribution throughout the entire human body. In healthy volunteers, there existed synchronous interactions of dopaminergic neurons between the GI organs and PD-related brain nuclei. Whereas the PD patients seemed to have lost this regulation, suggesting a potential disruption in the “brain-GI” connections of the disease.
Acknowledgements: This work was supported by grants from Clinical Research Plan of SHDC (16CR2020A).