Somatostatin Receptor Imaging of Inflammation in Arterial Disease

Jan 25, 2023
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Authors:
Ćorović A, Wall C, Nus M, et al.
Citation:
Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis. J Am Coll Cardiol 2023;81:336-354.
Summary By:
Debabrata Mukherjee, MD, FACC

Quick Takes

  • Somatostatin receptor 2 (SST2) receptors are expressed by inflammatory macrophages, as well as pericytes and perivascular adipocytes within inflamed arteries of patients with large vessel vasculitis (LVV).
  • SST2 receptors can be detected with PET/MRI using re-purposed radioligands such as 68Ga-DOTATATE or 18F-FET-βAG-TOCA, which could offer a useful clinical adjunct for diagnosis and monitoring of disease activity and therapeutic efficacy in LVV.
  • Additional prospective studies are indicated to compare the sensitivity and specificity of SST2 PET/MRI across the clinical spectrum of disease activity and responses to treatment.

Study Questions:

What is the role of somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in large vessel vasculitis (LVV)?

Methods:

The investigators conducted a prospective, observational cohort study and 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-nuclei RNA sequencing. Group comparisons were made using the Kruskal-Wallis test and Wilcoxon matched-pairs signed rank test. Receiver-operating characteristic analysis was used to assess diagnostic accuracy and identify optimal tissue-to-blood ratio (TBR) thresholds based on the Youden index.

Results:

Sixty-one participants (LVV, n = 27; recent atherosclerotic myocardial infarction ≤2 weeks, n = 25; control subjects with an oncological indication for imaging, n = 9) were included. Index vessel SST2 maximum TBR (TBRmax) 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 (FDG) PET/CT 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) (p = 0.04; 22.3%) reduction in SST2 TBRmax after 9.3 (standard deviation 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 co-expressed pro-inflammatory markers.

Conclusions:

The authors report that SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV.

Perspective:

This study reports that SST2 receptors are expressed by inflammatory macrophages, as well as pericytes and perivascular adipocytes within inflamed arteries of patients with LVV. Furthermore, SST2 receptors can be detected with PET/MRI using re-purposed radioligands such as 68Ga-DOTATATE or 18F-FET-βAG-TOCA, which could offer a useful clinical adjunct for diagnosis and monitoring of disease activity and therapeutic efficacy in LVV. Of note, while 18F-FDG PET is an important component of the diagnostic workup of patients with suspected LVV, it may be less useful for tracking response to therapy or monitoring long-term disease activity. Additional prospective studies are indicated to compare the sensitivity and specificity of SST2 PET/MRI across the clinical spectrum of disease activity and responses to treatment.

Clinical Topics: Noninvasive Imaging, Vascular Medicine, Computed Tomography, Magnetic Resonance Imaging, Nuclear Imaging

Keywords: Adipocytes, Atherosclerosis, Autoradiography, Diagnostic Imaging, Electrons, Fluorodeoxyglucose F18, Inflammation, Macrophages, Magnetic Resonance Imaging, Myocardial Infarction, Pericytes, Receptors, Somatostatin, Somatostatin, Tomography, X-Ray Computed, Vascular Diseases, Vasculitis


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