Unfortunately, high F-FDG background signal in the healthy heart makes it challenging to visualize inflammation in the coronaries or in the infarct itself 12, 13, 14. In the context of cardiac imaging, the absence of F-FDG signal is indicative of cardiomyocyte loss after myocardial infarction 11. In fact, in vitro 9 and recent in vivo atherosclerosis studies 10 indicate that vascular F-FDG signal might also originate from cells other than plaque macrophages, including non-immune cells. First and foremost, being a glucose analog, F-FDG is taken up by metabolically active cells and is not necessarily specific for inflammatory cells. Nevertheless, several limitations are associated with F-FDG’s use for cardiovascular inflammation imaging. Originally developed as a cancer PET tracer, F-fluorodeoxyglucose (F-FDG) is also the most commonly used inflammation tracer in cardiovascular disease, both in the context of atherosclerosis and cardiac ischemia 7, 8. As cardiovascular inflammation is rapidly developing into a therapeutic target, quantitative positron emission tomography (PET) inflammation imaging of the heart and vasculature is rapidly gaining momentum. In the past two decades, pre-clinical and clinical studies 2, 3, 4, 5, 6 have uncovered inflammation’s critical role in atherosclerotic plaque formation and the onset of cardio- and cerebrovascular events. Our results support further investigations on the use of DOTATATE to assess cardiovascular inflammation as a complementary readout to the widely used F-FDG.Ĭardiovascular disease is the principal cause of morbidity and mortality worldwide 1. In conclusion, we present a detailed, head-to-head comparison of the novel SST2-specific tracer DOTATATE and the validated metabolic tracer F-FDG for the evaluation of inflammation in small animal models of cardiovascular disease. In a translational PET/MRI study in atherosclerotic rabbits, we then compared Ga-DOTATATE and F-FDG for the assessment of aortic inflammation, combined with ex vivo radiometric assays and near-infrared imaging of macrophage burden. In both models, Cu-DOTATATE demonstrated preferential accumulation in macrophages with respect to other myeloid cells, while F-FDG was taken up by macrophages and other leukocytes. In atherosclerotic mice, Cu-DOTATATE PET aortic signal, but not F-FDG PET, was higher compared to controls (SUV max 1.1, IQR, 0.9–1.3 and 0.5, IQR, 0.5–0.6, respectively, N = 4, p = 0.0286). In mice subjected to myocardial infarction, in vivo Cu-DOTATATE PET showed higher differential uptake between infarcted (SUV max 1.3, IQR, 1.2–1.4, N = 4) and remote myocardium (SUV max 0.7, IQR, 0.5–0.8, N = 4, p = 0.0286), and with respect to controls (SUV max 0.6, IQR, 0.5–0.7, N = 4, p = 0.0286), than F-FDG PET.

To evaluate differences in the tracers’ cellular specificity, we performed ensuing ex vivo flow cytometry and gamma counting. Additionally, we performed in vivo PET/CT experiments in mice with atherosclerosis, mice subjected to myocardial infarction and control animals, using both Cu-DOTATATE and F-FDG. DOTATATE’s pharmacokinetics and timed biodistribution were determined in control and atherosclerotic mice and rabbits by ex vivo gamma counting of blood and organs. For translational PET/MRI rabbit studies, we employed the more widely clinically used Ga-labeled DOTATATE, which was approved by the FDA in 2016. For mouse experiments, we labeled DOTATATE with the long-lived isotope Cu to enable studying the tracer’s mode of action by complementing in vivo PET/CT experiments with thorough ex vivo immunological analyses. In the current study, we performed a detailed, head-to-head comparison of DOTATATE-based radiotracers and F-FDG in mouse and rabbit models of cardiovascular inflammation. While the former is a widely applied metabolic tracer, DOTATATE is a relatively new PET tracer targeting the somatostatin receptor 2 (SST2). Clinically, two approved PET tracers hold great potential for inflammation imaging in cardiovascular patients, namely FDG and DOTATATE. In recent years, cardiovascular immuno-imaging by positron emission tomography (PET) has undergone tremendous progress in preclinical settings.

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