Arene radiofluorination enabled by photoredox-mediated halide interconversion

Area of Science:

• Radiochemistry
• Medical Imaging
• Organic Synthesis

Background:

• Positron emission tomography (PET) relies on molecular probes for in vivo imaging and drug development.
• Current methods for radiofluorination, especially for creating C-18F bonds, are limited in efficiency, simplicity, and site-selectivity.
• Developing facile labeling methods is crucial for advancing PET probe discovery and application.

Purpose of the Study:

• To introduce a novel and efficient method for constructing C-18F bonds in electron-rich halo(hetero)arenes.
• To enable site-selective radiofluorination using readily available aryl halide precursors.
• To demonstrate the utility of this method for rapid PET probe diversification and synthesis of established PET agents.

Main Methods:

• Direct halide/fluorine-18 conversion under mild photoredox conditions.
• Utilizing [18F]F- for site-selective introduction into aryl halide precursors.
• Application to the synthesis of an [18F]-labeled O-methyl tyrosine library and L-[18F]FDOPA.

Main Results:

• Successful construction of C-18F bonds in a broad spectrum of halo(hetero)arenes.
• Site-selective radiofluorination achieved under mild photoredox conditions.
• Demonstrated rapid PET probe diversification and high-yielding synthesis of L-[18F]FDOPA.

Conclusions:

• The developed method offers an efficient and simple approach for C-18F bond formation.
• This strategy facilitates the preparation of diverse PET imaging agents.
• The method provides a valuable tool for advancing molecular probe development in PET imaging.