Imaging diabetic cardiomyopathy in a type 1 diabetic rat model using ¹⁸F-FEPPA PET

Objective: Diabetic patients often experience chronic inflammation and fibrosis in their cardiac tissues, highlighting the pressing need for the development of sensitive diagnostic methods for longitudinal assessment of diabetic cardiomyopathy. This study aims to evaluate the significance of an inflammatory marker known as translocator protein (TSPO) in a positron emission tomography (PET) protocol for longitudinally monitoring cardiac dysfunction in a diabetic animal model. Additionally, we compared the commonly used radiotracer, ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸F-FDG). Methods: Fourteen 7-week-old female Sprague-Dawley rats were used in this study. Longitudinal PET experiments were conducted using ¹⁸F-N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide (¹⁸F-FEPPA) (n = 3), the TSPO radiotracer, and ¹⁸F-FDG (n = 3), both before and after the onset of diabetes. Histological and immunohistochemical staining assays were also conducted in both the control (n = 4) and diabetes (n = 4) groups. Results: Results indicated a significant increase in cardiac tissue uptake of ¹⁸F-FEPPA after the onset of diabetes (P < 0.05), aligning with elevated TSPO levels observed in diabetic animals according to histological data. Conversely, the uptake of ¹⁸F-FDG in cardiac tissue significantly decreased after the onset of diabetes (P < 0.05). Conclusion: These findings suggest that ¹⁸F-FEPPA can function as a sensitive probe for detecting chronic inflammation and fibrosis in the cardiac tissues of diabetic animals.