5-(4-(2-[¹⁸F]fluoroethoxy)phenyl)-1-(2,4-dichlorophenyl)-4-cyano-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹⁸F]JHU88868), a Novel radioligand for PET imaging of cannabinoid type 1 receptors

PET imaging of cannabinoid type 1 receptor (CB1) is important for assessment of the receptor role in many neurological and psychiatric disorders. 5-(4-(2-[¹⁸F]fluoroethoxy)phenyl)-1-(2,4-dichlorophenyl)-4-cyano-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([¹⁸F]JHU88868), an analog of the radiotracer of choice for PET imaging of CB1 receptors in humans [¹¹C]JHU75528 ([¹¹C]OMAR), with a longer half-life exhibits high CB1 binding affinity (K_i = 16, 17 nM) and moderate lipophilicity. An efficient synthesis of JHU88868 and its bromoethoxy derivative for radiolabeling are presented. [¹⁸F]-2 ([¹⁸F]JHU88868) was prepared in one step by a Kryptofix-assisted radiofluorination of the corresponding bromo-precursor in DMSO solution at 135°C using a nucleophilic fluorination radiochemistry box with radiochemical yield of 1-5%, radiochemical purity greater than 95% and the average specific activity of 4000 mCi/ mol at the end-of-synthesis.