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Lookup NU author(s): Dr Gary Reynolds
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The AuthorsBackground: 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. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810)
Author(s): Corovic A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jorgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM
Publication type: Article
Publication status: Published
Journal: Journal of the American College of Cardiology
Year: 2023
Volume: 81
Issue: 4
Pages: 336-354
Print publication date: 31/01/2023
Online publication date: 23/01/2023
Acceptance date: 24/10/2022
Date deposited: 31/01/2023
ISSN (print): 0735-1097
ISSN (electronic): 1558-3597
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.jacc.2022.10.034
DOI: 10.1016/j.jacc.2022.10.034
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