Fluorine-18: Radiochemistry and Target-Specific PET Molecular Probes Design

Abstract

The positron emission tomography (PET) molecular imaging technology has gained universal value as a critical tool for assessing biological and biochemical processes in living subjects. The favorable chemical, physical, and nuclear characteristics of fluorine-18 (97% β+ decay, 109.8 min half-life, 635 keV positron energy) make it an attractive nuclide for labeling and molecular imaging. It stands that 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is the most popular PET tracer. Besides that, a significantly abundant proportion of PET probes in clinical use or under development contain a fluorine or fluoroalkyl substituent group. For the reasons given above, 18F-labeled radiotracer design has become a hot topic in radiochemistry and radiopharmaceutics. Over the past decades, we have witnessed a rapid growth in 18F-labeling methods owing to the development of new reagents and catalysts. This review aims to provide an overview of strategies in radiosynthesis of [18F]fluorine-containing moieties with nucleophilic [18F]fluorides since 2015.

Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

“…Bioactive compounds labeled with 18 F could be used as tracers for non-invasive visualization and quantification of molecular interactions, receptor binding, metabolism, and other dynamic processes in living organisms. PET is a significate application of fluorination using 18 F tracers, and so many works have been reported over the past decades 113 , 114 , 115 , 116 , 117 .…”

[18F]Fluspidine—A PET Tracer for Imaging of σ1 Receptors in the Central Nervous System

“…In nuclear medicine, fluorine-18-labeled PET tracers have emerged as powerful tools for non-invasive molecular imaging. The physical and nuclear properties of fluorine-18 (t ½ = 109.8 min, 97% e + ( β + ) decay, e + energy 635 keV) [ 49 ] and its availability in cyclotron facilities render fluorine-18 superior to other radionuclides. The broad applicability of fluorine-18 was driven by the development of novel radiofluorination methods [ 50 ] and the automate-supported production of PET tracers.…”

Strategies for Nucleophilic C(sp3)–(Radio)Fluorination

“…In the context of reagent profiles, sources of fluoride are practical in that they are often inexpensive, bench-stable, and readily accessible. ,, Furthermore, the development of these reagents has obviated the need for F 2 gas, which posed a significant safety and practicality challenge in fluorination chemistry. , Furthermore, fluoride reagents do not behave as oxidants, whereas electrophilic fluorinating reagents are generally oxidizing. Thus, nucleophilic fluorination strategies present orthogonal functional group compatibility by comparison to electrophilic strategies. , Finally, from a radiochemical perspective, [ 18 F]­fluoride is the preferred reagent for PET tracer synthesis. ,− …”