title: 18-kDa translocator protein ligand18F-FEMPA: Biodistribution and uptake into atherosclerotic plaques in mice.
abstract: Radioligands of 18-kDa translocator protein (TSPO) expressed on activated macrophages are a potential approach for imaging of inflammation in atherosclerosis. We evaluated a novel TSPO-targeted tracer18F-FEMPA for the detection of atherosclerotic plaque inflammation in mice.
  
  
  
  The distribution kinetics of18F-FEMPA was evaluated by in vivo PET/CT imaging.18F-FEMPA uptake was compared in atherosclerotic (LDLR-/-ApoB100/100, n = 10) and healthy mice (C57BL/6 N, n = 7) ex vivo at twenty minutes post-injection. Biodistribution was analyzed from harvested tissue samples, and aortas were sectioned for autoradiography. Aortas of LDLR-/-ApoB100/100mice showed large, macrophage-rich atherosclerotic plaques. In vivo,18F-FEMPA showed rapid blood clearance but no difference in aortic uptake between atherosclerotic and healthy mice. In the mice studied ex vivo at 20 minutes post-injection, quantification of radioactivity in the whole aorta showed 1.3-fold higher18F-FEMPA accumulation in atherosclerotic than healthy mice (P = .028). Autoradiography showed higher tracer uptake in plaque areas with high macrophage content as compared with areas of no macrophages (count densities 190 ± 54 vs 40 ± 13 PSL/mm2, P < .001), but the uptake in the plaques was not higher than in the normal vessel wall (230 ± 78 PSL/mm2). In vitro blocking showed specific accumulation in mouse and human atherosclerotic plaques. Immunohistochemistry confirmed co-localization of TSPO and macrophages.
  
  
  
  18F-FEMPA shows rapid blood clearance and uptake in the mouse aorta. Uptake in atherosclerotic plaques correlated with the amount of macrophages, but did not exceed that in the normal vessel wall.
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Hellberg
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Johanna M U
authors.initials: JMU
authors.lastname: Silvola
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Max
authors.initials: M
authors.lastname: Kiugel
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku Center for Disease Modeling, University of Turku, Turku, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Liljenbäck
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Savisto
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Xiang-Guo
authors.initials: XG
authors.lastname: Li
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Thiele
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Lehmann
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Heinrich
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Vollmer
authors.affiliation: Department of Surgery, University of Turku, Turku, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Hakovirta
authors.affiliation: Department of Pathology, Turku University Hospital, Turku, Finland.
authors.forename: V Jukka O
authors.initials: VJO
authors.lastname: Laine
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, Turku University Hospital, Turku, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku Center for Disease Modeling, University of Turku, Turku, Finland.|Turku PET Centre, Turku University Hospital, Turku, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. antti.saraste@utu.fi.|Turku PET Centre, Turku University Hospital, Turku, Finland. antti.saraste@utu.fi.|Heart Center, Turku University Hospital and University of Turku, Turku, Finland. antti.saraste@utu.fi.|Institute of Clinical Medicine, University of Turku, Turku, Finland. antti.saraste@utu.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: C000602344:(18F)FEMPA; D015415:Biomarkers; C463819:Bzrp protein, mouse; D006845:Hydrocarbons, Fluorinated; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA
keywords: 18-kDa translocator protein; 18F-FEMPA; Atherosclerosis; PET/CT imaging; inflammation