[¹⁸F]BCPP-BF-PET as an imaging tool for mitochondrial dysfunction in diabetic pancreatopathy and nephrotoxicity

[¹⁸F]BCPP-BF-PET imaging of mitochondrial complex I was validated as a biomarker of hyperglycaemia- and hyperlipidaemia-induced pancreatic and renal dysfunction in a type 2 diabetes mellitus (T2DM) animal model.

Male Zucker diabetic fatty (ZDF) (Fatty) rats as a T2DM model and lean ZDF (Lean) rats as controls were subjected to [¹⁸F]BCPP-BF-PET imaging at 5, 8, 16, and 26 weeks of age. Blood biochemical parameters were assessed at all ages, and the kidney and pancreas were dissected after PET measurement for morphological assessments at 16 and 26 weeks of age.

Blood insulin and triglyceride levels were elevated in Fatty rats at 5 weeks of age and peaked at 8 weeks, followed by an increase in blood glucose and urea nitrogen levels at 16 weeks and thereafter. [¹⁸F]BCPP-BF uptake by the pancreas and kidneys was lower in Fatty rats than in Lean rats after 5 and 8 weeks of age, and thereafter. Pancreatic [¹⁸F]BCPP-BF uptake was inversely correlated with blood glucose and triglyceride levels as early as 5 weeks of age. In the pancreatic islets, a lower density of insulin-positive cells was detected in Fatty rats at 16 weeks of age, which was positively correlated with pancreatic [¹⁸F]BCPP-BF uptake. Renal [¹⁸F]BCPP-BF uptake and blood urea nitrogen indicated inverse correlations at 8 weeks of age and older, and the uptake and fibrotic areas revealed an inverse correlation at 16 weeks of age.

This study demonstrates the applicability of [¹⁸F]BCPP-BF-PET as a non-invasive biomarker for diagnosing hyperglycaemia- and hyperlipidaemia-induced pancreatic and renal damage in T2DM in the early phase of diabetes.