Non-invasive imaging of sympathetic innervation of the pancreas in individuals with type 2 diabetes.

Aims/hypothesis: Compromised pancreatic sympathetic innervation has been suggested as a factor involved in both immune-mediated beta cell destruction and endocrine dysregulation of pancreatic islets. To further explore these intriguing findings, new techniques for in vivo assessment of pancreatic innervation are required. This is a retrospective study that aimed to investigate whether the noradrenaline (norepinephrine) analogue C-hydroxy ephedrine (C-HED) could be used for quantitative positron emission tomography (PET) imaging of the sympathetic innervation of the human pancreas.

Methods: In 25 individuals with type 2 diabetes and 64 individuals without diabetes, all of whom had previously undergone C-HED-PET/CT because of pheochromocytoma or paraganglioma (or suspicion thereof), the C-HED standardised uptake value (SUV), C-HED specific binding index (SBI), pancreatic functional volume (FV, in ml), functional neuronal volume (FNV, calculated as SUV × FV), specific binding index with functional volume (SBI FV, calculated as SBI × FV) and attenuation on CT (HU) were investigated in the entire pancreas, and additionally in six separate anatomical pancreatic regions.

Results: Generally, C-HED uptake in the pancreas was high, with marked individual variation, suggesting variability in sympathetic innervation. Moreover, pancreatic CT attenuation (HU) (p<0.001), C-HED SBI (p=0.0049) and SBI FV (p=0.0142) were lower in individuals with type 2 diabetes than in individuals without diabetes, whereas C-HED SUV (p=0.15), FV (p=0.73) and FNV (p=0.30) were similar.

Conclusions/interpretation: We demonstrate the feasibility of using C-HED-PET for non-invasive assessment of pancreatic sympathetic innervation in humans. These findings warrant further prospective evaluation, especially in individuals with theoretical defects in pancreatic sympathetic innervation, such as those with type 1 diabetes.