RT Journal Article SR Electronic T1 Automated Synthesis and Preliminary Evaluation of 18F-FDPA for Cardiac Inflammation Imaging in Rats after Myocardial Infarction JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 323 OP 323 VO 61 IS supplement 1 A1 Tiantian Mou A1 Jing Tian A1 Yi Tian A1 Junqi Li A1 Wei Dong A1 Xia Lu A1 Ziwei Zhu A1 Hongzhi Mi A1 Xiang Li A1 Xiaoli Zhang YR 2020 UL http://jnm.snmjournals.org/content/61/supplement_1/323.abstract AB 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