The pharmacological mechanisms focusing on chiral isomer of ibuprofen are not fully understood. Only the (S)-isomer of ibuprofen inhibits cyclooxygenases, which mediates the generation of prostanoids and thromboxanes. Consequently, (S)-isomers represent a major promoter of the anti-inflammatory effect, and the effects of the (R)-isomers have not been widely discussed. However, more recently, the cyclooxygenase-independent pharmacological effects of ibuprofen have been elucidated. Pharmacokinetic studies with individual isomers of ibuprofen by positron emission tomography should aid our understanding of the pharmacological mechanisms of ibuprofen. The efficient 11C-labeling of ibuprofen for chiral separation via the TBAF-promoted α-[11C]methylation was achieved by using DMSO rather than THF as the reaction solvent. The robust production of the radiochemically labile 11C-labeled ibuprofen ester was realized by the protective effect of DMSO on radiolysis. After intravenous injection of each enantiomer of [11C]ibuprofen, significantly high radioactivity was observed in the joints of arthritis mice when compared to the levels observed in normal mice. However, the high accumulation was equivalent between the enantiomers, indicating that ibuprofen is accumulated in the arthritic joints regardless of the expression of cyclooxygenases.

We describe the synthesis of 11C-labeled α-aminoisobutyric acid 2 from iodo[11C]methane and methyl N-(diphenylmethylen)-d,l-alaniate (5). The tetrabutylammonium fluoride (TBAF)-promoted α-[11C]methylation of sterically hindered analog 5 was a key step in our synthesis process. Total radiochemical conversion of 2 was high and a remote-controlled synthesis was carried out. A comparative tumor positron emission tomography (PET) imaging study using the same model mouse showed higher uptake of 2 than with 11C-labeled methionine and [18F] fluorodeoxyglucose (FDG).We describe the synthesis of 11C-labeled α-aminoisobutyric acid 2 from iodo[11C]methane and methyl N-(diphenylmethylen)-d,l-alaniate (5). The tetrabutylammonium fluoride (TBAF)-promoted α-[11C]methylation of sterically hindered analog 5 was a key step in our synthesis process. Total radiochemical conversion of 2 was high and a remote-controlled synthesis was carried out. A comparative tumor positron emission tomography (PET) imaging study using the same model mouse showed higher uptake of 2 than with 11C-labeled methionine and [18F] fluorodeoxyglucose (FDG).

Tetrabutylammonium fluoride-promoted α-[11C]methylation of α-arlylesters was developed. The method was amenable to the remote-controlled synthesis of 11C-labeled ibuprofen.Tetrabutylammonium fluoride-promoted α-[11C]methylation of α-arlylesters was developed. The method was amenable to the remote-controlled synthesis of 11C-labeled ibuprofen.

The nitroaldol reaction of nitro[11C]methane and formaldehyde using EtOH and EtONa efficiently provided 2-nitro[11C]ethanol in 3 min. The nitro group reduction in the presence of NiCl2 and NaBH4 in MeOH followed by purification using semi-preparative HPLC using 10% EtOH aqueous solution as an eluent proved to be a practical and accessible method for the synthesis of 2-amino[2-11C]ethanol.A practical and accessible method for the synthesis of 2-amino[2-11C]ethanol is reported.

The synthesis of (R,S)-[4-11C]baclofen, the first 11C-labeled GABAB agonist, was demonstrated via Michael addition of nitro[11C]methane as a key step. A tetrabutylammonium fluoride promoted Michael addition of nitro[11C]methane to methyl p-chlorocinnamate, followed by the nitro-group reduction in the presence of NiCl2 and NaBH4 in aqueous MeOH and alkaline hydrolysis yielded (R,S)-[4-11C]baclofen in 36.4 ± 1.8% radiochemical conversion in three steps within 20 min.

The labelling synthesis of ethyl nitro[2-11C]acetate, a synthetic intermediate feasible for 11C-labelled PET tracers, by C-carboxylation of [11C]MeNO2 with 1-ethoxycarbonylbenzotriazole, and its simple application are presented.