Aromatic radiofluorination of the diaryliodonium tosylate precursor with [¹⁸F]fluoride ions has been applied successfully to access [¹⁸F]flumazenil in high radiochemical yields of 67.2 ± 2.7% (decay corrected). The stability and reactivity of the diaryliodonium tosylate precursor plays a key role in increasing the production of ¹⁸F-labelled molecules under the fluorine-18 labelling condition. Various conditions were explored for the preparation of [¹⁸F]flumazenil from different diaryliodonium tosylate precursors. Optimum incorporation of [¹⁸F]fluoride ions in the 4-methylphenyl-mazenil iodonium tosylate precursor (5f) was achieved at 150 °C for 5 min by utilizing 4 mg of the precursor, K_2.2.2/K₂CO₃ complex, and the radical scavenger in N,N-dimethylformamide. This approach was extended to a viable method for use in automated synthesis with a radiochemical yield of 63.5 ± 3.2% (decay corrected, n = 26) within 60.0 ± 1.1 min. [¹⁸F]Flumazenil was isolated by preparative HPLC after the reaction was conducted under improved conditions and exhibited sufficient specific activity of 370–450 GBq μmol⁻¹, with a radiochemical purity of >99%, which will be suitable for human PET studies.

A new fluorine-substituted ligand, compound1(CB251), with a very high affinity (Ki = 0.27 ± 0.09 nM) and selectivity for the 18-kDa translocator protein (TSPO), is presented as an attractive biomarker for the diagnosis of neuroinflammation, neurodegeneration and tumour progression. To test compound1as a TSPO PET imaging agentin vivo, 2-(2-(4-(2-[¹⁸F]fluoroethoxy)phenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide ([¹⁸F]1; [¹⁸F]CB251) was synthesized by nucleophilic aliphatic substitution in a single-step radiolabelling procedure with a 11.1 ± 3.5% (n = 14, decay corrected) radiochemical yield and over 99% radiochemical purity. In animal PET imaging studies, [¹⁸F]CB251 provided a clearly visible image of the inflammatory lesion with the binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BP_ND1.83 ± 0.18), in a neuroinflammation rat model based on the unilateral stereotaxic injection of lipopolysaccharide (LPS), comparable to that of [¹¹C]PBR28 (BP_ND1.55 ± 0.41). [¹⁸F]CB251 showed moderate tumour uptake (1.96 ± 0.11%ID/g at 1 h post injection) in human glioblastoma U87-MG xenografts. These results suggest that [¹⁸F]CB251 is a promising TSPO PET imaging agent for neuroinflammation and TSPO-rich cancers.