Radiosynthesis and preclinical evaluation of [18F]FEM as a potential novel PET probe for tumor imaging. Issue 12 (15th June 2020)

• Record Type: Journal Article
• Authors: Jiang, Yanping; Zhou, Wenlan; Hu, Kongzhen; Han, Yanjiang; Sun, Penghui; Wang, Quanshi; Li, Guiping; Wu, Hubing; Tang, Ganghua; Huang, Shun
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 12(2020)
• Publication Date: 2020-06-15
• Subjects: [18F]FEM 2-(2-[18F]fluoroethoxy)ethyl 4-methylbenzenesulfonate -- PET positron emission tomography -- PBS phosphate-buffered saline -- MS mouse serum -- WHO World Health Organization -- T/M tumor-to-muscle -- BBB blood brain barrier -- CT computed tomography -- [18F]FDG 2-deoxy-2-[18F]fluoro-d-glucose -- [18F]FES 16-alpha-[18F]fluoroestradiol -- FAPIs fibroblast activator inhibitors -- [18F]FETs 2-[18F]fluoroethyl tosylate -- [18F]FEEM 2-(2-(2-[18F]fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate -- radio-HPLC radio-high performance liquid chromatography -- % ID/g percent injected dose per gram -- ROIs regions of interest -- TACs time-activity curves -- p.i. post-injection -- B/M brain-to-muscle; Alkylating agent -- [18F]FEM -- Positron emission tomography (PET) -- Tumor imaging; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127200
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Synthesis of [ 18 F]FEM as a potential novel PET probe for tumor imaging. [ 18 F]FEM can specifically accumulate at the tumor site of five different tumor models. [ 18 F]FEM can quickly cross the blood brain barrier (BBB) and quickly fade out. Abstract: In the 21st century, the incidence and mortality of cancer, one of the most challenging diseases in the world, have rapidly increased. The purpose of this study was to develop 2-(2-[ 18 F]fluoroethoxy)ethyl 4-methylbenzenesulfonate ([ 18 F]FEM) as a positron emission tomography (PET) agent for tumor imaging. In this study, [ 18 F]FEM was synthesized with a good radiochemical yield (45.4 ± 5.8%), high specific radioactivity (over 25 GBq/μmol), and commendable radiochemical purity (over 99%). The octanol/water partition coefficient of [ 18 F]FEM was 1.44 ± 0.04. The probe demonstrated good stability in vitro (phosphate-buffered saline (PBS) and mouse serum (MS)), and binding specificity to five different tumor cell lines (A549, PC-3, HCC827, U87, and MDA-MB-231). PET imaging of tumor-bearing mice showed that [ 18 F]FEM specifically accumulated at the tumor site of the five different tumor cell lines. The average tumor-to-muscle (T/M) ratio was over 2, and the maximum T/M values reached about 3.5. The biodistribution and dynamic PET imaging showed that most probes were metabolized by the liver, whereas a small part was metabolized by the kidney. Moreover, dynamic brain images and quantitative data showed [ 18 F]FEM can quickly cross the blood brain barrier (BBB) and quickly fade out, thereby suggesting it may be a promising candidate probe for the imaging of brain tumors. The presented results demonstrated that [ 18 F]FEM is a promising probe for tumor PET imaging.