title: Detection of Atherosclerotic Inflammation by68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging.
abstract: BACKGROUND
  Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.
  
  
  OBJECTIVE
  This study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation.
  
  
  METHODS
  We confirmed68Ga-DOTATATE binding in macrophages and excised carotid plaques.68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis.
  
  
  RESULTS
  Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific68Ga-DOTATATE ligand binding to SST2receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02).68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003).68Ga-DOTATATE mTBRmaxpredicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmaxdifferentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary68Ga-DOTATATE PET scans were readable in all patients.
  
  
  CONCLUSIONS
  We validated68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Tarkin
authors.affiliation: Heart Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Joshi
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Evans
authors.affiliation: Department of Vascular and Endovascular Surgery, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Chowdhury
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nichola L
authors.initials: NL
authors.lastname: Figg
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Aarti V
authors.initials: AV
authors.lastname: Shah
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Lakshi T
authors.initials: LT
authors.lastname: Starks
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Abel
authors.initials: A
authors.lastname: Martin-Garrido
authors.affiliation: Department of Radiology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Roido
authors.initials: R
authors.lastname: Manavaki
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Yu
authors.affiliation: Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Rhoda E
authors.initials: RE
authors.lastname: Kuc
authors.affiliation: Department of Hematology, University of Cambridge, and National Health Service Blood and Transport, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Luigi
authors.initials: L
authors.lastname: Grassi
authors.affiliation: Department of Hematology, University of Cambridge, and National Health Service Blood and Transport, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Roman
authors.initials: R
authors.lastname: Kreuzhuber
authors.affiliation: Department of Hematology, University of Cambridge, and National Health Service Blood and Transport, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Myrto A
authors.initials: MA
authors.lastname: Kostadima
authors.affiliation: Department of Hematology, University of Cambridge, and National Health Service Blood and Transport, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Mattia
authors.initials: M
authors.lastname: Frontini
authors.affiliation: Division of Neurosurgery, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kirkpatrick
authors.affiliation: Department of Vascular and Endovascular Surgery, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Coughlin
authors.affiliation: Department of Radiology, University of Cambridge, Cambridge, United Kingdom; Department of Radiology, Hammersmith Hospital, London, United Kingdom.
authors.forename: Deepa
authors.initials: D
authors.lastname: Gopalan
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Fryer
authors.affiliation: Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: John R
authors.initials: JR
authors.lastname: Buscombe
authors.affiliation: Institute of Nuclear Medicine, University College London, London, United Kingdom.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Groves
authors.affiliation: Department of Hematology, University of Cambridge, and National Health Service Blood and Transport, Cambridge Biomedical Campus, Cambridge, United Kingdom; Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Warburton
authors.affiliation: Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Davenport
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom. Electronic address: jhfr2@cam.ac.uk.
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000000981:diagnostic imaging*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds; D000072078:Positron Emission Tomography Computed Tomography; D017481:Receptors, Somatostatin / Q000032:analysis / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D019788:Fluorodeoxyglucose F18; C513399:gallium Ga 68 dotatate
keywords: atherosclerosis; inflammation; macrophages; molecular imaging; positron emission tomography; somatostatin receptor