Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography

Clinical events in atherosclerosis are largely driven by inflammation. Molecular imaging of atherosclerosis can potentially identify high-risk lesions, help guide treatment and illuminate the underlying biology of the disease. 18F-fluorodeoxyglucose (18F-FDG) PET is the gold-standard nuclear molecular imaging technique with well-established roles in atherosclerosis imaging. However, the arterial 18F-FDG signal is non-specific, although it is related to increased macrophage activity with contributions from hypoxia and angiogenesis. Coronary artery imaging with 18F-FDG is particularly difficult, mainly due to high background myocardial cell 18F-FDG uptake, which obscures interpretation of the coronary signal. Efforts to suppress myocardial 18F-FDG uptake with dietary manipulation are challenging for patients and have limited efficacy.

PET tracers currently used in cancer imaging, such as 68Ga-DOTATATE, are potentially more specific for inflammation and also lack myocardial muscle uptake. 68Ga-DOTATATE might therefore be better suited than 18F-FDG for imaging inflammation, particularly within the coronary arteries. The VISION study is a prospective, observational study designed to investigate the biology of plaque inflammation in atherosclerosis, using PET imaging with the somatostatin receptor ligand 68Ga-DOTATATE. 50 subjects with atherosclerosis will undergo sequential PET/CT imaging with 68Ga-DOTATATE and 18F-FDG, along with contrast angiography of the carotid and coronary arteries. Autoradiography and immunohistochemistry of excised carotid plaques will be used to validate the imaging data. If successful, 68Ga-DOTATATE imaging will offer a cheaper, more specific non-invasive measure of inflammation than 18F- FDG, particularly in the coronary arteries. This opens up the possibility of better risk stratification for patients with atherosclerosis and could provide a non-invasive platform to test the effects of novel anti-atherosclerosis drugs.

Inclusion criteria

• Age ≥40 years of age
• Can provide written, fully informed consent
• Have had a transient ischemic attack (TIA) or stroke within the preceding four weeks due to carotid artery atherosclerosis; or have ≥30% carotid artery or epicardial coronary artery stenosis

Exclusion criteria

• Renal impairment (eGFR<30mls/min)
• History of contrast nephropathy
• Atrial fibrillation
• Any condition, in the opinion of the investigator, which prevents the participant from lying flat during scanning
• Women of childbearing potential
• Inability to provide written informed consent
• Haemorrhagic stroke within 3 months of study entry
• Total occlusion of a culprit carotid artery
• Any medical condition, vital sign or laboratory value that, in the opinion of the investigator, makes the subject ineligible for inclusion