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

被引：42

作者：

Corovic, Andrej ^{[1
]}

Wall, Christopher ^{[1
]}

Nus, Meritxell ^{[1
]}

Gopalan, Deepa ^{[2
,3
]}

Huang, Yuan ^{[4
]}

Imaz, Maria ^{[1
]}

Zulcinski, Michal ^{[5
]}

Peverelli, Marta ^{[1
,6
]}

Uryga, Anna ^{[1
]}

Lambert, Jordi ^{[1
]}

Bressan, Dario ^{[7
]}

Maughan, Robert T. ^{[6
]}

Pericleous, Charis ^{[6
]}

Dubash, Suraiya ^{[8
,9
]}

Jordan, Natasha ^{[10
]}

Jayne, David R. ^{[11
]}

Hoole, Stephen P. ^{[12
]}

Calvert, Patrick A. ^{[12
]}

Dean, Andrew F. ^{[13
]}

Rassl, Doris ^{[14
]}

Barwick, Tara ^{[2
,9
]}

Iles, Mark ^{[5
]}

Frontini, Mattia ^{[15
]}

Hannon, Greg ^{[7
]}

Manavaki, Roido ^{[16
]}

Fryer, Tim D. ^{[17
]}

Aloj, Luigi ^{[16
]}

Graves, Martin J. ^{[16
]}

Gilbert, Fiona J. ^{[16
]}

Dweck, Marc R. ^{[18
]}

Newby, David E. ^{[18
]}

Fayad, Zahi A. ^{[19
]}

Reynolds, Gary ^{[20
]}

Morgan, Ann W. ^{[5
]}

Aboagye, Eric O. ^{[9
]}

Davenport, Anthony P. ^{[1
]}

Jorgensen, Helle F. ^{[1
]}

Mallat, Ziad ^{[1
]}

Bennett, Martin R. ^{[1
]}

Peters, James E. ^{[21
]}

Rudd, James H. F. ^{[1
]}

Mason, Justin C. ^{[6
]}

Tarkin, Jason M. ^{[1
,6
]}

机构：

[1] Univ Cambridge, Sect Cardioresp Med, Cambridge, England

[2] Imperial Coll Healthcare Natl Hlth Serv NHS Trust, Dept Radiol, London, England

[3] Cambridge Univ Hosp NHS Trust, Dept Radiol, Cambridge, England

[4] Univ Cambridge, Engn & Phys Sci Res Council, Ctr Math Imaging Healthcare, Cambridge, England

[5] Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, England

[6] Imperial Coll London, Natl Heart & Lung Inst, Vasc Sci, London, England

[7] Canc Res UK Cambridge Inst, Cambridge, England

[8] Univ Coll London NHS Trust, Dept Oncol, London, England

[9] Imperial Coll London, Dept Surg & Canc, London, England

[10] Cambridge Univ Hosp NHS Trust, Dept Rheumatol, Cambridge, England

[11] Univ Cambridge, Dept Med, Cambridge, England

[12] Royal Papworth Hosp NHS Trust, Dept Cardiol, Cambridge, England

[13] Cambridge Univ Hosp NHS Trust, Dept Histopathol, Cambridge, England

[14] Royal Papworth Hosp NHS Trust, Dept Histopathol, Cambridge, England

[15] Univ Exeter, Inst Biomed & Clin Sci, Med Sch, Exeter, England

[16] Univ Cambridge, Dept Radiol, Cambridge, England

[17] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[18] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Scotland

[19] Icahn Sch Med Mt Sinai, BioMed Engn & Imaging Inst, New York, NY USA

[20] Univ Newcastle, Dept Rheumatol, Newcastle, England

[21] Imperial Coll London, Ctr Inflammatory Dis, London, England

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2023年 / 81卷 / 04期

基金：

英国惠康基金; 英国工程与自然科学研究理事会; 英国医学研究理事会; 美国国家卫生研究院; 英国科研创新办公室;

关键词：

atherosclerosis; giant cell arteritis; inflammation; molecular imaging; somatostatin receptor; Takayasu arteritis; POSITRON-EMISSION-TOMOGRAPHY;

D O I：

10.1016/j.jacc.2022.10.034

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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/).

引用

页码：336 / 354

页数：19

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