Aliphatic 18F‐Radiofluorination: Recent Advances in the Labeling of Base‐Sensitive Substrates

• Published in: ChemMedChem Vol. 16; no. 17; pp. 2612 - 2622
• Main Authors: Bratteby, Klas, Shalgunov, Vladimir, Herth, Matthias Manfred
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 06.09.2021
• Subjects: aliphatic; Aliphatic compounds; base sensitivity; Fluorination; Fluorine; Fluorine isotopes; fluorine-18; Labeling; Positron emission; Radioactive tracers; Radiochemistry; Radiolabelling; Reviews; SN2; Substrates; Tomography
• DOI: 10.1002/cmdc.202100303
• ISSN: 1860-7179

Aliphatic fluorine‐18 radiolabeling is the most commonly used method to synthesize tracers for PET‐imaging. With an increasing demand for 18F‐radiotracers for clinical applications, new labeling strategies aiming to increase radiochemical yields of established tracers or, more importantly, to enable 18F‐labeling of new scaffolds have been developed. In recent years, increased attention has been focused on the direct aliphatic 18F‐fluorination of base‐sensitive substrates in this respect. This minireview gives a concise overview of the recent advances within this field and aims to highlight the advantages and limitations of these methods. With a growing interest in fluorine‐18, the number of radiopharmaceuticals produced is likely to increase in the coming years. However, in the development of new labeling techniques, the factor of regulating the basicity of the reaction is often overlooked. This can be detrimental or even prevent labeling of many precursors. In this minireview, we focus on strategies to decrease the basicity in carrying out aliphatic 18F‐fluorinations.