Evaluating N‐difluoromethyltriazolium triflate as a precursor for the synthesis of high molar activity [18F]fluoroform

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 64; no. 12; pp. 466 - 476
• Main Authors: Pees, Anna, Vosjan, Maria J. W. D., Chai, Jin Young, Cha, Hyojin, Chi, Dae Yoon, Windhorst, Albert D., Vugts, Danielle J.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-10-2021; John Wiley and Sons Inc
• Subjects: [18F]fluoroform; [18F]trifluoromethylation; Bioactive compounds; Biological activity; Chemistry Techniques, Synthetic; Chlorofluorocarbons, Methane - chemical synthesis; Chlorofluorocarbons, Methane - chemistry; Emitters; Fluorine; Fluorine isotopes; Fluorine Radioisotopes - chemistry; fluorine‐18; high molar activity; Labeling; Mesylates - chemistry; Positron emission; Positron emission tomography; Precursors; Radiochemistry; Radiochemistry - methods; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Synthesis; Tomography; Triazoles - chemical synthesis; Triazoles - chemistry; triazolium precursor; Trifluoromethane; high molar activity; fluorine-18; triazolium precursor; [18F]fluoroform; [18F]trifluoromethylation
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3939

The trifluoromethyl group is a prominent motif in biologically active compounds and therefore of great interest for the labeling with the positron emitter fluorine‐18 for positron emission tomography (PET) imaging. Multiple labeling strategies have been explored in the past; however, most of them suffer from low molar activity due to precursor degradation. In this study, the potential of 1‐(difluoromethyl)‐3‐methyl‐4‐phenyl‐1H‐1,2,3‐triazol‐3‐ium triflate as precursor for the synthesis of the [18F]trifluoromethylation building block [18F]fluoroform with high molar activity was investigated. The triazolium precursor was reacted under various conditions with [18F]fluoride, providing [18F]fluoroform with radiochemical yields (RCY) and molar activities (Am) comparable and even superior with already existing methods. Highest molar activities (Am = 153 ± 14 GBq/μmol, dc, EOS) were observed for the automated procedure on the Neptis® perform module. Due to its easy handling and good RCY and Am in the [18F]fluoroform synthesis, the triazolium precursor is a valuable alternative to already known precursors.
This article describes the evaluation of N‐difluoromethyltriazolium triflate as a new precursor for high molar activity [18F]fluoroform. The triazolium precursor was reacted under various conditions with [18F]fluoride, providing [18F]fluoroform with good radiochemical yields and high molar activities.