Abstract 16641: 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<0.0001), and link with Framingham risk score (r=0.53 [0.3-0.7], p<0.0001). While vascular 68Ga-DOTATATE and 18F-FDG TBRs were correlated (r=0.73, p<0.0001), coronary 18F-FDG imaging was only possible in 36% of patients owing to excessive myocardial signal overspill—which did not occur with 68Ga-DOTATATE (Fig 1). Unlike 18F-FDG, high target specificity of 68Ga-DOTATATE for pro-inflammatory (M1) macrophages was confirmed using RNA sequencing and quantitative PCR for SST2. 68Ga-DOTATATE exhibited specific autoradiographic receptor binding in macrophage-rich (CD68 positive) regions of ruptured carotid plaques, with good co-localization to clinical images and SST2 immunohistochemistry.
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.
Author Disclosures: J.M. Tarkin: None. F.R. Joshi: None. N.R. Evans: None. M.M. Chowdhury: None. N.L. Figg: None. A.V. Shah: None. L.T. Starks: None. R. Manavaki: None. A. Martin-Garrido: None. E. Yu: None. R.E. Kuc: None. L. Grassi: None. R. Kreuzhuber: None. M. Kostadima: None. M. Frontini: None. W.H. Ouwehand: None. A.M. Groves: None. D. Gopalan: None. P.J. Kirkpatrick: None. P.A. Coughlin: None. J.R. Buscombe: None. T.D. Fryer: None. M.R. Bennett: None. E.A. Warburton: None. A.P. Davenport: None. J.H. Rudd: None.
- © 2016 by American Heart Association, Inc.