PT  - JOURNAL ARTICLE
AU  - Zhequan Fu
AU  - Qingyu Lin
AU  - Bingxin Hu
AU  - Yingying Zhang
AU  - Weijia Chen
AU  - Jing Zhu
AU  - Yanzhao Zhao
AU  - Hak Soo Choi
AU  - Hongcheng Shi
AU  - Dengfeng Cheng
TI  - P2X7 PET Radioligand <sup>18</sup>F-PTTP for Differentiation of Lung Tumor from Inflammation
AID  - 10.2967/jnumed.118.222547
DP  - 2019 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 930--936
VI  - 60
IP  - 7
4099  - http://jnm.snmjournals.org/content/60/7/930.short
4100  - http://jnm.snmjournals.org/content/60/7/930.full
SO  - J Nucl Med2019 Jul 01; 60
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.