Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE autoradiographic, immunohistochemical and flow cytometric studies in apoE-deficient mice

Abstract

Background: The rupture of atherosclerotic plaques is triggered by inflammation. Specific detection of inflammation is therefore the focus of many investigations. Noninvasive imaging methods, such as positron emission tomography (PET), also are suited for this purpose. (68)Ga-DOTATATE is a (68)Ga-labeled radiotracer with specific affinity to somatostatin receptor subtype-2 (SSTR-2). SSTR-2 was found specifically expressed on human macrophages/monocytes.

Objective: We aimed to confirm the distribution of SSTR-2 in inflammatory plaques, and to assess its co-localization with macrophages within the plaques. We also assessed (68)Ga-DOTATATE uptakes in plaques by autoradiography.

Method: Apolipoprotein E (ApoE)-/- mice on a high-cholesterol diet were injected with (68)Ga-DOTATATE. The animals were sacrificed and aorta sections were examined using autoradiography and immunohistochemistry. Furthermore, expression of SSTR-2 was analyzed by flow cytometry. Western blot was conducted to assess SSTR-2 regulation in basal and lipopolysaccharide (LPS)-activated state. To evaluate the specificity of the (68)Ga-DOTATATE, the sections were pre-incubated with monoclonal SSTR-2 antibody before autoradiography.

Result: Autoradiographic imaging showed uptake of (68)Ga-DOTATATE co-localized with the macrophage-rich plaques by immunohistochemical examination. A high expression of SSTR-2 on macrophages was found by flow cytometry and western blot. Stimulation with lipopolysaccharide did not alter expression of SSTR-2 in macrophages.

Conclusion: Due to its specific binding to macrophages, (68)Ga-DOTATATE might be a suitable radiotracer for the evaluation of inflammatory activity in unstable plaques.

Keywords: (68)Ga-DOTATATE; Atherosclerosis; Autoradiography; Inflammation; Somatostatin receptor subtype2.