Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis

BACKGROUND Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-bAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of #2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: $0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxy-glucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 +/- 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 +/- 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. CONCLUSIONS SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810) (J Am Coll Cardiol 2023;81:336-35 4) (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).