Pancreatic functional damage and reversion to normoglycaemia after STZ-induced diabetes in minipigs: evidence of preserved coupling between [¹⁸F]FDOPA PET and glucose regulation

Abstract Purpose To evaluate the relationship between pancreatic functional damage and reversion to normoglycaemia after streptozotocin (STZ)-induced diabetes in adult minipigs, and the associations of 6-[¹⁸F]fluoro-L-3,4-dihydroxyphenylalanine ([¹⁸F]FDOPA) uptake with insulin-positive area and glucose dynamics. Methods Twelve adult male minipigs (15–22 kg, 10 months old) with STZ-induced (150 mg/kg) pancreatic β-cell injury were followed for 30 days. Continuous glucose monitoring assessed interstitial glucose and glycaemic variability. Reversion was defined as fasting interstitial glucose at day 30 within the cohort baseline range (40–66 mg/dL). [¹⁸F]FDOPA PET/CT was performed at baseline, day 15, and day 30 (± 3 days). Pancreatic functional damage was estimated from changes in the pancreatic-to-splenic uptake ratio (SUVr), and insulin-positive area was quantified histologically. Results Three of 12 minipigs (25%) achieved reversion to normoglycaemia. At day 30, reversion animals had lower interstitial glucose (46.0 vs. 130.5 mg/dL, p = 0.013) and glycaemic variability (CV 15.5% vs. 23.7%, p = 0.021). Pancreatic tail SUVrmean was higher in the reversion group at day 15 (1.9 [1.4–1.9] vs. 1.3 [1.2–1.4], p = 0.033). Pancreatic head [¹⁸F]FDOPA uptake correlated with insulin-positive area (r ≈ 0.74, p < 0.05), whereas functional damage alone did not fully discriminate between groups. Conclusion Reversion to normoglycaemia after STZ-induced diabetes in minipigs represents a dynamic functional phenotype that is not solely explained by the magnitude of pancreatic injury. [¹⁸F]FDOPA PET may reflect residual endocrine function and highlights a non-linear relationship between pancreatic damage and metabolic outcome.