[¹⁸F]Difluorocarbene for positron emission tomography.

Area of Science:

• Nuclear imaging
• Radiochemistry
• Organic synthesis

Background:

• Total-body positron emission tomography (PET) expands molecular imaging research.
• Fluorine-18 (¹⁸F) radiochemistry has advanced, but ¹⁸F-difluoromethylation remains challenging.
• The difluoromethyl group is vital for pharmaceutical drug discovery.

Purpose of the Study:

• To introduce a general solution for ¹⁸F-difluoromethylation.
• To develop a versatile [¹⁸F]difluorocarbene reagent for nuclear imaging.
• To enable high molar activity labeling of difluoromethylated molecules.

Main Methods:

• Utilized carbene chemistry for nuclear imaging applications.
• Designed a novel [¹⁸F]difluorocarbene reagent for facile accessibility and high molar activity.
• Investigated isotopic dilution effects on precursor electronics.
• Demonstrated versatility through O-H, S-H, and N-H insertions, and cross-coupling reactions.

Main Results:

• Developed a general solution for ¹⁸F-difluoromethylation.
• Achieved high molar activity labeling.
• Showcased reagent versatility with various functional groups including (thio)phenols, N-heteroarenes, and aryl boronic acids.
• Successfully labeled complex, biologically relevant molecules and radiotracers.

Conclusions:

• The new [¹⁸F]difluorocarbene reagent overcomes previous limitations in ¹⁸F-difluoromethylation.
• This method provides facile access to high molar activity difluoromethylated compounds.
• The reagent's versatility and impact are demonstrated in labeling complex molecules for PET imaging and drug discovery.