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.
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.