On the Risk of 18F-Regioisomer Formation in the Copper-Free Radiofluorination of Aryliodonium Precursors

Aryliodonium precursors are widely applied for copper-free labeling of positron emission tomography (PET) tracers with fluorine-18. We assessed F-18-fluoroarene regioisomer formation in examples of these labeling methods. Aryliodonium ylides derived from Meldrum's acid bearing para electron-donating groups react with [F-18]-fluoride in acetonitrile to produce regioisomeric F-18-fluoroarenes via a competing aryne pathway. Regioisomer formation is decreased or absent in DMF. Analytically checking for the absence of the F-18-regioisomer from any particular PET tracer radiosynthesis using these or similar methods is recommended.

Automated summary

In this study, we investigated the use of aryliodonium precursors for copper-free labeling of PET tracers with fluorine-18. We found that regioisomeric F-18-fluoroarenes can be formed in certain labeling methods. The reaction between aryliodonium ylides derived from Meldrum's acid with para electron-donating groups and [F-18]-fluoride in acetonitrile produces regioisomeric F-18-fluoroarenes via a competing aryne pathway. The formation of regioisomers is decreased or absent in DMF. It is recommended to analytically check for the absence of the F-18-regioisomer in any specific PET tracer radiosynthesis using these or similar methods.