%0 Journal Article %A Tiantian Mou %A Jing Tian %A Yi Tian %A Junqi Li %A Wei Dong %A Xia Lu %A Ziwei Zhu %A Hongzhi Mi %A Xiang Li %A Xiaoli Zhang %T Automated Synthesis and Preliminary Evaluation of 18F-FDPA for Cardiac Inflammation Imaging in Rats after Myocardial Infarction %D 2020 %J Journal of Nuclear Medicine %P 323-323 %V 61 %N supplement 1 %X 323Objectives: In this study, a translocator protein 18 kDa (TSPO) targeted radiotracer, N,N-diethyl-2-(2-(4-18F-fluorophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (18F-FDPA), was automated synthetized and evaluated as a potential cardiac inflammation imaging agent. Methods: 18F-FDPA was radiolabeled automatically by a one-step nucleophilic reaction with a stable spirocyclic iodonium ylide as the precursor. Various reaction conditions, such as the amount of tetrabutylammonium methanesulfonate (TBAOMs), reaction temperature, and labeling time were systematically optimized. For normal rats (n=3), 18F-FDPA dynamic PET/CT imaging studies were performed, and the time-activity curves of interested organs were drawn. Dynamic PET/CT scans with both 18F-FDPA and 13N-NH3 and static 18F-FDG PET/CT imaging were performed 1 week after ligation of the proximal left anterior descending artery in rats. Mean standardized uptake values (SUVs) of 18F-FDPA in the myocardial infarction (MI) central region, the peri-infarction and the remote regions were analyzed. Target to background ratios (TBRs) of SUVs in peri-infarction/remote region and infarction/remote region in the heart were calculated. After PET/CT imaging studies, the hearts were harvested and stained with hematoxylin and eosin (H&E). Results: The amount of TBAOMs and the volume/proportion of water were crucial for F-18 labeling. After precise optimization, the total synthesis time of 18F-FDPA was 68 min using CFN-MPS200 module. The non-decay corrected radiochemical yields (RCYs) were 19.9 ± 1.7% (n = 3). The radiochemical purities were over 99%. The molar activities were 169.7 ± 46.5 GBq/μmol. In normal rats, 18F-FDPA showed high and stable heart uptake and fast clearance from other organs, including lungs. In MI rats, a severe perfusion defect with significantly reduced 13N-NH3 activity was observed in the apex and anterior wall while the extent of reduced 18F-FDG uptake was smaller than that in 13N-NH3 images. Localized elevated 18F-FDPA uptake in the peri-infarction region matched with high 18F-FDG uptake was observed in all MI rats. At 25, 35, 45 and 55 min post-injection (p.i.), the SUVs of 18F-FDPA in the peri-infarction region were comparable (8.27, 8.30, 8.26 and 8.08, respectively, P = 0.977) and the TBRs of peri-infarction/remote region were sustained (1.21 ± 0.13, 1.26 ± 0.09, 1.29 ± 0.16 and 1.31 ± 0.19, respectively, P=0.824). At 55 min p.i., the SUV of 18F-FDPA in the MI region (3.38 ± 0.92) was significantly lower than that in the remote region, while significantly higher than that of muscle (SUV was 0.62 ± 0.01) or other organs with barely TSPO. Both the infarct and the peri-infarction regions were infiltrated with massive inflammatory cells. Conclusions: 18F-FDPA was successfully automated synthesized with good RCYs, high molar activities and short synthesis time. The fast clearance of 18F-FDPA from non-target organs and the stable uptake in the heart offered a wide time window for cardiac imaging. High 18F-FDPA activity in the peri-infarction region and a large number of inflammatory cells revealed by pathology, which indicated it could be as a potential cardiac inflammation imaging agent. TSPO was highly expressed in both normal cardiomyocytes and inflammatory cells. Acknowledgements: This project was sponsored by the Beijing Hospitals Authority Youth Programme (20190606) and the National Natural Science Foundation of China (81871377, 81571717, 81301251). View this table:The elution efficiency of 18F-FDPA from the QMA cartridge using different kinds of stock solution %U