S-EPMC5381358 - Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. - OmicsDI

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Detection of Atherosclerotic Inflammation by 68Ga-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. OBJECTIVES: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 confirmed 68Ga-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, specific 68Ga-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 68Ga-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 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 [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]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 [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients. CONCLUSIONS:We validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-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).

SUBMITTER: Tarkin JM

PROVIDER: S-EPMC5381358 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Detection of Atherosclerotic Inflammation by <sup>68</sup>Ga-DOTATATE PET Compared to [<sup>18</sup>F]FDG PET Imaging.

Tarkin Jason M JM Joshi Francis R FR Evans Nicholas R NR Chowdhury Mohammed M MM Figg Nichola L NL Shah Aarti V AV Starks Lakshi T LT Martin-Garrido Abel A Manavaki Roido R Yu Emma E Kuc Rhoda E RE Grassi Luigi L Kreuzhuber Roman R Kostadima Myrto A MA Frontini Mattia M Kirkpatrick Peter J PJ Coughlin Patrick A PA Gopalan Deepa D Fryer Tim D TD Buscombe John R JR Groves Ashley M AM Ouwehand Willem H WH Bennett Martin R MR Warburton Elizabeth A EA Davenport Anthony P AP Rudd James H F JH

Journal of the American College of Cardiology 20170401 14

<h4>Background</h4>Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([<sup>18</sup>F]FDG PET), [<sup>18</sup>F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.<h4>Objectives</h4>This study tested the efficacy of gallium-68-labeled DOTATATE (<sup>68</sup>Ga-DOTATATE), a somatostatin receptor subtype-2 (SST<sub>2</sub>)-binding PET tracer ...[more]

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