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 11 C-hydroxy ephedrine ( 11 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 11 C-HED-PET/CT because of pheochromocytoma or paraganglioma (or suspicion thereof), the 11 C-HED standardised uptake value (SUV mean ), 11 C-HED specific binding index (SBI), pancreatic functional volume (FV, in ml), functional neuronal volume (FNV, calculated as SUV mean × 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, 11 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), 11 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 11 C-HED SUV mean ( p =0.15), FV ( p =0.73) and FNV ( p =0.30) were similar. Conclusions/interpretation We demonstrate the feasibility of using 11 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. Graphical Abstract