title: [(18)F]Fluoromethyl-PBR28 as a potential radiotracer for TSPO: preclinical comparison with [(11)C]PBR28 in a rat model of neuroinflammation.
abstract: To develop radiotracer for the translocator protein 18 kDa (TSPO) in vivo, N-(2-[(18)F]fluoromethoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([(18)F]1, [(18)F]fluoromethyl-PBR28) was prepared by incorporating of fluorine-18 into triazolium triflate-PBR28 precursor (7). The radiochemical yield of [(18)F]1 after HPLC purification was 35.8 ± 3.2% (n = 11, decay corrected). Radiotracer [(18)F]1 was found to be chemically stable when incubated in human serum for 4 h at 37 °C. Both aryloxyanilide analogs (1 and 2) behaved similarly in terms of lipophilicity and in vitro affinity for TSPO. Here, both radiotracers were directly compared in the same inflammatory rat to determine whether either radiotracer provides more promising in vivo TSPO binding. Uptake of [(18)F]1 in the inflammatory lesion was comparable to that of [(11)C]PBR28, and [(18)F]1 rapidly approached the highest target-to-background ratio at early imaging time (35 min postinjection versus 85 min postinjection for [(11)C]PBR28). These results suggest that [(18)F]1 is a promising radiotracer for imaging acute neuroinflammation in rat. In addition, our use of a triazolium triflate precursor for [(18)F]fluoromethyl ether group provides the convenient application for radiofluorination of radiotracer containing a methoxy group.
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine , Seoul, Korea.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.forename: Bom Sahn
authors.initials: BS
authors.lastname: Kim
authors.forename: Chansoo
authors.initials: C
authors.lastname: Park
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Jung
authors.forename: Youn Woo
authors.initials: YW
authors.lastname: Lee
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Dae Yoon
authors.initials: DY
authors.lastname: Chi
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D002250:Carbon Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D004195:Disease Models, Animal; D004660:Encephalitis / Q000473:pathology*; D005462:Fluorine Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines