Triazole-Based Radioligands for PET of P2XR: Syntheses, Conformational Studies, and Preliminary Autoradiographic Evaluation of .

The P2X receptor is an emerging target for molecular imaging of inflammation in the brain and peripheral tissues. In this work, we focus on five triazole-based ligands with high affinity and selectivity for P2X receptors (, , , , and ), which are amenable to autoradiography and positron emission tomography (PET) imaging. We studied the phenomenon of conformational and rotational changes of these molecules by NMR and calculations. The reaction of ligands and with [F]-fluoride resulted in an isotopic exchange on the pyrimidine ring, leaving the halogen atoms on the acyl moieties intact. The reaction yielded with a radiochemical yield as high as 27% and a molar activity as high as 152 GBq/μmol. Quantitative autoradiography with in sagittal mouse brain cryostat sections indicated a maximum specific binding ( ) of 15.8 ± 2.8 pmol/g of wet weight and a dissociation constant ( ) of 16.6 ± 5.1 nM. Thus, we present the first synthesis of by isotopic exchange and confirm its specific binding at mouse brain P2X receptors, which should warrant its use in animal and human PET investigations.