5-(4-(2-[ F]fluoroethoxy)phenyl)-1-(2,4-dichlorophenyl)-4-cyano-N- (piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ F]JHU88868), a Novel Radioligand for PET Imaging of Cannabinoid Type 1 Receptors

Title: 5-(4-(2-[ F]fluoroethoxy)phenyl)-1-(2,4-dichlorophenyl)-4-cyano-N- (piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ F]JHU88868), a Novel Radioligand for PET Imaging of Cannabinoid Type 1 Receptors

Volume: 2 Issue: 3

Author(s): Yongjun Gao, Hayden T. Ravert, Robert F. Dannals and Andrew G. Horti

Affiliation:

Keywords: Cannabinoid receptor, positron emission tomography (PET), radiofluorination

Abstract: 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 (Ki = 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/μmol at the end-ofsynthesis.

Cite this article as:

Gao Yongjun, Ravert T. Hayden, Dannals F. Robert and Horti G. Andrew, 5-(4-(2-[ F]fluoroethoxy)phenyl)-1-(2,4-dichlorophenyl)-4-cyano-N- (piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ F]JHU88868), a Novel Radioligand for PET Imaging of Cannabinoid Type 1 Receptors, Current Radiopharmaceuticals 2009; 2 (3) . https://dx.doi.org/10.2174/1874471010902030195