68Ga-DOTATATE PET Outperforms 18F-FDG PET for Imaging Vascular Inflammation in Atherosclerosis

Introduction: Activated macrophages express somatostatin receptor subtype-2 (SST2) within unstable and high-risk atherosclerotic plaques. Hypothesis: We tested the hypothesis that 68Ga-DOTATATE, a clinical SST2 PET tracer, is a more specific macrophage marker than 18F-FDG, and is superior for coronary imaging. Methods: In this prospective clinical study, 42 patients with stable or unstable atherosclerosis underwent 68Ga-DOTATATE and 18F-FDG PET imaging of carotid, aorta and coronary arteries. PET signals were evaluated against clinical data, and comprehensively validated using molecular and histological methods. Results: 68Ga-DOTATATE maximum tissue-to-background ratios (TBR) were higher in culprit vs. corresponding non-culprit arteries in patients with acute coronary syndrome (median 2.9 [IQR 2.7-4.1] vs. 2.6 [2.0-3.0], p=0.008), and transient ischemic attack or stroke (2.0 [1.7-2.1] vs. 1.8 [1.5-2.1], p=0.003). 68Ga-DOTATATE signals also showed good diagnostic accuracy to detect high-risk coronary CT features (ROC AUC 0.86, p Conclusion: 68Ga-DOTATATE PET represents a novel, non-invasive method for measuring vascular inflammation, which is cell-specific, and with excellent coronary image contrast, outperforms the current gold-standard.