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

Andrej Ćorović, Christopher Wall, Meritxell Nus, Deepa Gopalan, Yuan Huang, Maria Imaz, Michal Zulcinski, Marta Peverelli, Anna Uryga, Jordi Lambert, Dario Bressan, Robert T. Maughan, Charis Pericleous, Suraiya Dubash, Natasha Jordan, David R. Jayne, Stephen P. Hoole, Patrick A. Calvert, Andrew F. Dean, Doris RasslTara Barwick, Mark Iles, Mattia Frontini, Greg Hannon, Roido Manavaki, Tim D. Fryer, Luigi Aloj, Martin J. Graves, Fiona J. Gilbert, Marc R. Dweck, David E. Newby, Zahi A. Fayad, Gary Reynolds, Ann W. Morgan, Eric O. Aboagye, Anthony P. Davenport, Helle F. Jørgensen, Ziad Mallat, Martin R. Bennett, James E. Peters, James H.F. Rudd, Justin C. Mason, Jason M. Tarkin

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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-βAG-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-fluorodeoxyglucose 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.

Original languageEnglish
Pages (from-to)336-354
Number of pages19
JournalJournal of the American College of Cardiology
Volume81
Issue number4
DOIs
StatePublished - 31 Jan 2023

Keywords

  • atherosclerosis
  • giant cell arteritis
  • inflammation
  • molecular imaging
  • somatostatin receptor
  • Takayasu arteritis

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