title: [18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain.
abstract: We evaluated the efficacy of 2-[5-(4-[(18)F]fluoroethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methyl-N-phenylacetamide] ([(18)F]FEBMP) for positron emission tomography (PET) imaging of translocator protein (18 kDa, TSPO). Dissection was used to determine the distribution of [(18)F]FEBMP in mice, while small-animal PET and metabolite analysis were used for a rat model of focal cerebral ischemia. [(18)F]FEBMP showed high radioactivity uptake in mouse peripheral organs enriched with TSPO, and relatively high initial brain uptake (2.67 ± 0.12% ID/g). PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 ± 0.12, compared to non-injured striatum. Displacement with specific TSPO ligands lowered the accumulation levels in infarcts to those on the contralateral side. This suggests that the increased accumulation reflected TPSO-specific binding of [(18)F]FEBMP in vivo. Using a simplified reference tissue model, the binding potential on the infarcted area was 2.72 ± 0.27. Metabolite analysis in brain tissues showed that 83.2 ± 7.4% and 76.4 ± 2.1% of radioactivity was from intact [(18)F]FEBMP at 30 and 60 min, respectively, and that this ratio was higher than in plasma (8.6 ± 1.9% and 3.9 ± 1.1%, respectively). In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [(18)F]FEBMP. These findings suggest that [(18)F]FEBMP is a promising new tool for visualization of neuroinflammation.
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan ; 2. Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Anjani K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Ji
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.affiliation: 3. Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China .
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yiding
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: 3. Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China .
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001583:Benzoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002545:Brain Ischemia / Q000175:diagnosis* / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis*; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D051379:Mice; D059906:Neuroimaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000032:analysis; D011963:Receptors, GABA-A / Q000032:analysis*
chemical_list: D000083:Acetanilides; D001583:Benzoxazoles; C463819:Bzrp protein, mouse; D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C499229:TSPO protein, human; C069997:Tspo protein, rat
keywords: [18F]FEBMP; binding potential; neuroinflammation; rs6971 polymorphism; translocator protein (18 kDa)