Section of Cardiorespiratory Medicine, University of Cambridge, Cambridge, United Kingdom.
Department of Radiology, Imperial College Healthcare National Health Service (NHS) Trust, London, United Kingdom; Department of Radiology, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.
J Am Coll Cardiol. 2023 Jan 31;81(4):336-354. doi: 10.1016/j.jacc.2022.10.034.
Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.
We aimed to investigate somatostatin receptor 2 (SST) as a novel inflammation-specific molecular imaging target in LVV.
In a prospective, observational cohort study, in vivo arterial SST expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using Ga-DOTATATE and F-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.
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 SST 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 SST signal was not elevated in any of the control subjects. SST PET/MRI was generally consistent with F-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 SST maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST 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.
SST 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).
通过传统方法评估大动脉血管炎（LVV）的炎症活动可能具有挑战性。
我们旨在研究生长抑素受体 2（SST）作为 LVV 中新型炎症特异性分子成像靶标。
在一项前瞻性观察队列研究中，通过正电子发射断层扫描/磁共振成像（PET/MRI）使用 Ga-DOTATATE 和 F-FET-βAG-TOCA 评估动脉 SST 表达。使用免疫荧光显微镜；成像质谱细胞术；以及批量、单细胞和单核 RNA 测序进行成像靶标的离体映射。
共纳入 61 名参与者（LVV：n=27；近期动脉粥样硬化性心肌梗死<2 周：n=25；有影像学适应证的肿瘤患者：n=9）。活动/咕噜作响的 LVV 的指数血管 SST 最大组织与血液比为 61.8%（P<0.0001）高于非活动 LVV，比心肌梗死高 34.6%（P=0.0002），具有良好的诊断准确性（曲线下面积：≥0.86；两者均 P<0.001）。任何对照受试者的动脉 SST 信号均未升高。SST PET/MRI 与同时进行临床扫描的 LVV 患者的 F-氟脱氧葡萄糖 PET/计算机断层扫描成像基本一致，但大脑和心脏的背景信号非常低，允许不受阻碍地评估附近的冠状动脉、心肌和颅内动脉受累情况。LVV 的临床有效治疗与 9.3±3.2 个月后 SST 最大组织与血液比降低 0.49±0.24（均数标准误差[SEM]）（P=0.04；22.3%）相关。SST 表达定位于血管炎标本中的巨噬细胞、周细胞和血管周围脂肪细胞，通过放射自显影证实了特定的受体结合。表达 SSTR2 的巨噬细胞共表达促炎标志物。
SST PET/MRI 在 LVV 的诊断和治疗监测方面具有很大的潜力。（巨细胞和 Takayasu 动脉炎的正电子发射断层扫描成像[PITA]，NCT04071691；残留炎症和斑块进展长期评估[RIPPLE]，NCT04073810）。
