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

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. This study tested t...

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Published in:Journal of the American College of Cardiology 2017-04, Vol.69 (14), p.1774-1791
Main Authors: Tarkin, Jason M., Joshi, Francis R., Evans, Nicholas R., Chowdhury, Mohammed M., Figg, Nichola L., Shah, Aarti V., Starks, Lakshi T., Martin-Garrido, Abel, Manavaki, Roido, Yu, Emma, Kuc, Rhoda E., Grassi, Luigi, Kreuzhuber, Roman, Kostadima, Myrto A., Frontini, Mattia, Kirkpatrick, Peter J., Coughlin, Patrick A., Gopalan, Deepa, Fryer, Tim D., Buscombe, John R., Groves, Ashley M., Ouwehand, Willem H., Bennett, Martin R., Warburton, Elizabeth A., Davenport, Anthony P., Rudd, James H.F.
Format: Article
Language:English
Subjects:
atherosclerosis
inflammation
macrophages
molecular imaging
Original Investigation
positron emission tomography
somatostatin receptor
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Summary: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. 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. 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. 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 
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2017.01.060