title: Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer ¹⁸F-fluoromethylcholine.
abstract: BACKGROUND
  Diabetes is a risk factor for atherosclerosis associated with oxidative stress, inflammation and cell proliferation. The purpose of this study was to evaluate arterial choline uptake and its relationship to atherosclerotic inflammation in diabetic and non-diabetic hypercholesterolemic mice.
  
  
  METHODS
  Low-density lipoprotein-receptor deficient mice expressing only apolipoprotein B100, with or without type 2 diabetes caused by pancreatic overexpression of insulin-like growth factor II (IGF-II/LDLR(-/-)ApoB(100/100) and LDLR(-/-)ApoB(100/100)) were studied. Distribution kinetics of choline analogue (18)F-fluoromethylcholine ((18)F-FMCH) was assessed in vivo by positron emission tomography (PET) imaging. Then, aortic uptakes of (18)F-FMCH and glucose analogue (18)F-fluorodeoxyglucose ((18)F-FDG), were assessed ex vivo by gamma counting and autoradiography of tissue sections. The (18)F-FMCH uptake in atherosclerotic plaques was further compared with macrophage infiltration and the plasma levels of cytokines and metabolic markers.
  
  
  RESULTS
  The aortas of all hypercholesterolemic mice showed large, macrophage-rich atherosclerotic plaques. The plaque burden and densities of macrophage subtypes were similar in diabetic and non-diabetic animals. The blood clearance of (18)F-FMCH was rapid. Both the absolute (18)F-FMCH uptake in the aorta and the aorta-to-blood uptake ratio were higher in diabetic than in non-diabetic mice. In autoradiography, the highest (18)F-FMCH uptake co-localized with macrophage-rich atherosclerotic plaques. (18)F-FMCH uptake in plaques correlated with levels of total cholesterol, insulin, C-peptide and leptin. In comparison with (18)F-FDG, (18)F-FMCH provided similar or higher plaque-to-background ratios in diabetic mice.
  
  
  CONCLUSIONS
  Type 2 diabetes enhances the uptake of choline that reflects inflammation in atherosclerotic plaques in mice. PET tracer (18)F-FMCH is a potential tool to study vascular inflammation associated with diabetes.
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. saelhe@utu.fi.
authors: Sanna
authors: S
authors: Hellberg
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. johanna.silvola@utu.fi.
authors: Johanna M U
authors: JM
authors: Silvola
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. max.kiugel@utu.fi.
authors: Max
authors: M
authors: Kiugel
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. heidi.liljenback@utu.fi.|Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland. heidi.liljenback@utu.fi.
authors: Heidi
authors: H
authors: Liljenbäck
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. olli.metsala@utu.fi.
authors: Olli
authors: O
authors: Metsälä
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. tapio.viljanen@utu.fi.
authors: Tapio
authors: T
authors: Viljanen
authors: Genomics and Biomarkers Unit, National Institute for Health and Welfare, Haartmaninkatu 8, 00250, Helsinki, Finland. jari.metso@thl.fi.
authors: Jari
authors: J
authors: Metso
authors: Genomics and Biomarkers Unit, National Institute for Health and Welfare, Haartmaninkatu 8, 00250, Helsinki, Finland. matti.jauhiainen@thl.fi.
authors: Matti
authors: M
authors: Jauhiainen
authors: Department of Pathology and Forensic Medicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland. psaukko@utu.fi.
authors: Pekka
authors: P
authors: Saukko
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. pirjo.nuutila@utu.fi.|Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland. pirjo.nuutila@utu.fi.
authors: Pirjo
authors: P
authors: Nuutila
authors: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70210, Kuopio, Finland. seppo.ylaherttuala@uef.fi.|Science Service Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, Finland. seppo.ylaherttuala@uef.fi.
authors: Seppo
authors: S
authors: Ylä-Herttuala
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. juhani.knuuti@tyks.fi.|Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland. juhani.knuuti@tyks.fi.
authors: Juhani
authors: J
authors: Knuuti
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. anne.roivainen@utu.fi.|Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland. anne.roivainen@utu.fi.|Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland. anne.roivainen@utu.fi.
authors: Anne
authors: A
authors: Roivainen
authors: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. antti.saraste@utu.fi.|Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland. antti.saraste@utu.fi.|Heart Center, Turku University Hospital, Hämeentie 11, 20520, Turku, Finland. antti.saraste@utu.fi.
authors: Antti
authors: A
authors: Saraste
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging* / Q000378:metabolism; D001018:Aortic Diseases / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D006937:Hypercholesterolemia; D008264:Macrophages / Q000378:metabolism / Q000528:radiation effects; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058226:Plaque, Atherosclerotic; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C516370:fluoromethylcholine; D002794:Choline