1228664-35-4Relevant academic research and scientific papers
General method for the C-labeling of 2-arylpropionic acids and their esters: Construction of a PET tracer library for a study of biological events involved in COXs expression
Takashima-Hirano, Misato,Shukuri, Miho,Takashima, Tadayuki,Goto, Miki,Wada, Yasuhiro,Watanabe, Yasuyoshi,Onoe, Hirotaka,Doi, Hisashi,Suzuki, Masaaki
experimental part, p. 4250 - 4258 (2010/09/10)
Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate 11C radionuclide into various 2-arylpropionic acids that have a common methylated structure, particularly among nonsteroidal antiinflammatory drugs (NSAIDs). Thus, we developed a novel 11C-radiolabeling methodology based on rapid C[11C] methylation by the reaction of [11C]CH3I with enolate intermediates generated from the corresponding esters under basic conditions. One-pot hydrolysis of the above [11C]methylation products also allows the synthesis of desired 11C-incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [ 11C]Ibuprofen, [11C]Naproxen, [11C] Flurbiprofen, [11C]Fenoprofen, [11C]Ketoprofen, and [ 11C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)-induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [ 11C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general 11C-labeling of 2-arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression.
