Abstract 460: 64 Cu-DOTATATE for in vivo Positron Emission Tomography Imaging of Somatostatin Receptor 2 Expressing Macrophages in a Göttingen Minipig Model of Atherosclerosis

Abstract

Background: Somatostatin receptor subtype 2 (SSTR 2 ) is expressed by activated macrophages which are important effector cells in atherogenesis and a major constituent of atherosclerotic plaques. SSTR 2 can be targeted non-invasively in vivo using the tracer 64 Cu-DOTATATE and positron emission tomography (PET). Methods: Male castrated Göttingen minipigs were treated according to two diet regimes for 43 weeks: chow (lean control; n=1) or high-fat/high-cholesterol diet (HFHC, obese group; n=2). Plasma lipids: total cholesterol (TC) and triglycerides (TG) were measured and SSTR 2 expression was assessed using hybrid positron emission tomography/magnetic resonance (PET/MR) imaging of the abdominal aorta, one hour (range: 60-63 minutes) post injection with 200 MBq (range 202-214 MBq) of 64 Cu-DOTATATE. Consectutive regions of interest (ROIs) were drawn guided by MR to include vessel wall and lumen of the abdominal aorta to calculate standardized uptake values (SUVs). Target-to-background (TBR) ratios were calculated using right atrium SUVs for blood pool correction (SUV vessel /SUV right atrium = TBR) and reported as mean and maximal values (TBR mean ; TBR max ). Results: Three minipigs (age 17 months) were included and PET/MR was completed in all animals. Mean uptake of 64 Cu-DOTATATE was lowest for the abdominal aorta in the lean control: TBR mean = 0.44 and TBR max = 0.73 (range: TBR mean = 0.29 - 0.62; TBR max = 0.49 - 1.10) and highest in the HFHC group: TBR mean = 0.66 and TBR max = 1.28 (range: TBR mean = 0.26 - 1.38; TBR max = 0.39 - 3.19). Plasma lipids: lean control: TC = 1.34 mmol/L; TG = 0.38 mmol/L; HFHC group (mean values): TC = 18.7mmol/L (range: 11.6 - 25.8mmol/L); TG = 0.6 mmol/L (range: 0.37 - 0.83mmol/L). Conclusion: Non-invasive 64 Cu-DOTATATE PET/MR is feasible for assessment of SSTR 2 expression in a Göttingen minipig model of diet-induced atherosclerosis. Additional studies are needed including assessment of histology findings and gene expression to confirm the presence of activated macrophages in order to validate the use of 64 Cu-DOTATATE PET/MR in this model.