RT Journal Article SR Electronic T1 P2X7 PET Radioligand 18F-PTTP for Differentiation of Lung Tumor from Inflammation JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 930 OP 936 DO 10.2967/jnumed.118.222547 VO 60 IS 7 A1 Zhequan Fu A1 Qingyu Lin A1 Bingxin Hu A1 Yingying Zhang A1 Weijia Chen A1 Jing Zhu A1 Yanzhao Zhao A1 Hak Soo Choi A1 Hongcheng Shi A1 Dengfeng Cheng YR 2019 UL http://jnm.snmjournals.org/content/60/7/930.abstract AB Site-specific imaging agents play a key role in tumor targeting, but only a few agents are currently available for inflammation targeting. Since the P2X7 receptor (P2X7R) is a promising molecular target for inflammation, we evaluated the potential value of the 18F-labeled tracer 18F-PTTP (5-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-1-pyrimidin-2-yl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridin) for targeting P2X7Rs and thus differentiating inflammation from tumors. Methods: The radioligand 18F-PTTP was achieved by a 1-step 18F-trifluoromethylation reaction. The binding affinity of the ligand for P2X7R and its stability were evaluated in vitro. Blood pharmacokinetics tests and biodistribution studies were performed in vivo. Dynamic 18F-PTTP small-animal PET/CT imaging was performed for 60 min on A549 tumor–bearing mice and inflammation-model mice for targeting differentiation. Results:18F-PTTP was afforded with decay-corrected radiochemical yields of 2.5%–7.0%, specific activity of 296–370 MBq/μmol, and radiochemical purity over 95%. 18F-PTTP showed excellent stability in 0.9% NaCl and 0.1% bovine serum albumin, good affinity to RAW264.7 cells, and rapid blood clearance in mice. In inflammation-model mice, uptake of 18F-PTTP peaked at 5 min after injection and kept at an imageable level till 30 min, whereas no significant radioactivity uptake was found in tumor grafts till 1 h after injection. The specificity of 18F-PTTP was verified by blocking studies and histologic analysis. Conclusion: The current study provides compelling data that 18F-PTTP is a novel radioligand targeting P2X7R and has potential to screen new drugs, quantify peripheral inflammation, and distinguish inflammation from certain solid tumors.