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

• The Somatostain receptor-2 (SSTR-2) was determined in inflammatory plaques.
• SSTR-2 was founded co-localized with macrophages/monocytes within the plaques.
• 68Ga-DOTATATE uptake co-localized with macrophage-rich plaques in ApoE−/− mice.
• We proved the specificity of the 68Ga-DOTATATE accumulation by inhibition study.
• 68Ga-DOTATATE is a suitable tracer for inflammation evaluation in unstable plaques.

BackgroundThe 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. 68Ga-DOTATATE is a 68Ga-labeled radiotracer with specific affinity to somatostatin receptor subtype-2 (SSTR-2). SSTR-2 was found specifically expressed on human macrophages/monocytes.ObjectiveWe 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 68Ga-DOTATATE uptakes in plaques by autoradiography.MethodApolipoprotein E (ApoE)−/− mice on a high-cholesterol diet were injected with 68Ga-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 68Ga-DOTATATE, the sections were pre-incubated with monoclonal SSTR-2 antibody before autoradiography.ResultAutoradiographic imaging showed uptake of 68Ga-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.ConclusionDue to its specific binding to macrophages, 68Ga-DOTATATE might be a suitable radiotracer for the evaluation of inflammatory activity in unstable plaques.