ABSTRACT
INTRODUCTION: Atherosclerosis is prevalent globally, closely associated with dyslipidemia and other metabolic dysfunction. Early diagnosis of atherosclerosis is challenging due to limited diagnostic capabilities that need to be expanded with animal models with enhanced vascular biology like rats. Our previous research showed [111In] In-DANBIRT has potential as a diagnostic tool for detecting atherosclerosis in mice. The primary aim of the present study is to evaluate [111In] In-DANBIRT in a novel atherosclerotic rat with early- and late-stage atherosclerosis and metabolic disease. METHODS: We characterized metabolic and body composition differences in these novel dyslipidemic rats under different diets using serum chemistry and dual-energy X-ray absorptiometry (DEXA) scan, respectively. We performed 1-h post-injection in vivo molecular imaging of ApoE knockout, lean Zucker (LZ) male rats at baseline and followed them into 10 weeks of either normal or high-fat/cholesterol diet implementation (22 weeks of age). RESULTS: We identified significant differences in body composition and metabolic changes in ApoE knockout rats compared to ApoE wildtype rats. Our findings indicate an increased uptake of [111In] In-DANBIRT in ApoE knockout, lean Zucker (LZ) rats, particularly in the descending aorta, a location where early-stage atherosclerosis is commonly found. Our findings, however, also revealed that the ApoE knockout, Zucker diabetic fatty (ZDF) model has high mortality rate, which may be attributed to alterations of critical enzymes involved in regulating metabolism and liver function. CONCLUSION: Our results are highly encouraging as they demonstrated the potential of [111In] In-DANBIRT to detect early-stage atherosclerosis in rats that might otherwise go unnoticed by other methods, showcasing the high sensitivity of [111In] In-DANBIRT. Our future studies will aim to establish a viable T2D atherosclerosis model in rats with more advanced stages of the disease to further demonstrate the reliability of [111In] In-DANBIRT as a diagnostic tool for patients in all stages of atherosclerosis.
