Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F] FDG PET Imaging

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:69

Article

Tarkin, Jason M.¹  Joshi, Francis R.²  Evans, Nicholas R.³  Chowdhury, Mohammed M.⁴  Figg, Nichola L.¹  Shah, Aarti V.¹  Starks, Lakshi T.¹  Martin-Garrido, Abel¹  Manavaki, Roido⁵  Yu, Emma¹  Kuc, Rhoda E.⁶  Grassi, Luigi^7,8  Kreuzhuber, Roman^7,8  Kostadima, Myrto A.^7,8  Frontini, Mattia^7,8  Kirkpatrick, Peter J.⁹  Coughlin, Patrick A.⁴  Gopalan, Deepa^5,10  Fryer, Tim D.³  Buscombe, John R.¹¹  Groves, Ashley M.¹²  Ouwehand, Willem H.^7,8,13  Bennett, Martin R.¹  Warburton, Elizabeth A.³  Davenport, Anthony P.⁶  Rudd, James H. F.¹ 

[1] Univ Cambridge, Div Cardiovasc Med, Cambridge, England

[2] Rigshosp, Heart Ctr, Copenhagen, Denmark

[3] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[4] Addenbrookes Hosp, Dept Vasc & Endovasc Surg, Cambridge, England

[5] Univ Cambridge, Dept Radiol, Cambridge, England

[6] Univ Cambridge, Expt Med & Immunotherapeut, Cambridge, England

[7] Univ Cambridge, Dept Hematol, Cambridge Biomed Campus, Cambridge, England

[8] Natl Hlth Serv Blood & Transport, Cambridge Biomed Campus, Cambridge, England

[9] Addenbrookes Hosp, Div Neurosurg, Cambridge, England

[10] Hammersmith Hosp, Dept Radiol, London, England

[11] Addenbrookes Hosp, Dept Nucl Med, Cambridge, England

[12] UCL, Inst Nucl Med, London, England

[13] Wellcome Trust Sanger Inst, Dept Human Genet, Wellcome Trust Genome Campus, Hinxton, England

关键词: atherosclerosis;    inflammation;    macrophages;    molecular imaging;    positron emission tomography;    somatostatin receptor;   

DOI  :  10.1016/j.jacc.2017.01.060

来源: Elsevier

【 摘 要 】

BACKGROUND Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([F-18] FDG PET), [F-18] FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. OBJECTIVES This study tested the efficacy of gallium-68-labeled DOTATATE (Ga-68-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. METHODS We confirmed Ga-68-DOTATATE binding in macrophages and excised carotid plaques. Ga-68-DOTATATE PET imaging was compared to [F-18] FDG PET imaging in 42 patients with atherosclerosis. RESULTS Target SSTR2 gene expression occurred exclusively inproinflammatory M1 macrophages, specific Ga-68-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo Ga-68-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). Ga-68-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). Ga-68-DOTATATE mTBRmax predicted 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 [F-18] FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [F-18] FDG mTBRmax differentiated 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 [F-18] FDG spillover rendered coronary [F-18] FDG scans uninterpretable in 27 patients (64%). Coronary Ga-68-DOTATATE PET scans were readable in all patients. CONCLUSIONS We validated Ga-68-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that Ga-68-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [F-18] FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

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