SUV on somatostatin receptor (SSTR) PET/CT imaging as a biomarker for glucose metabolism related pancreatic function

Introduction: Due to an overexpression of somatostatin receptors (SSTRs) on the surface of neuroendocrine tumors (NETs), PET/CT using SSTR-binding radioligands has become an established imaging method in the clinical routine in patients with NET. However, SSTRs are also physiologically expressed in pancreatic islets of Langerhans. Several studies indicated somatostatin as a highly relevant paracrine signal in the regulation of hormone secretion from α- and β-cells and thus in the glucose metabolism. In human islets, the subtype SSTR2 out of SSTR1-5 is the predominant receptor in both α- and β-cells. The affinity to the different subtypes varies depending on the radioligand used, e.g. ⁶⁸Ga-DOTATATE, ⁶⁸Ga-DOTATOC and ¹⁸F-SiTATE have a high affinity to SSTR2, whereas ⁶⁸Ga-DOTANOC has a high affinity to SSTR2, 3 and 5.

With this study we aimed at investigating the potential role of SSTR PET/CT as a biomarker for glucose metabolism related pancreatic function.

Methods: Patients with no known pancreatic disease who were undergoing SSTR PET/CT for other reasons than imaging of the pancreas were included. The pancreas was delineated in the CT and the respective SUV_max and SUV_mean of the entire pancreas was determined in the PET. The HbA_1c, as a biomarker for glucose metabolism, at the time point of the PET/CT (± 2 weeks) was then correlated with the SUV_max and SUV_mean. This analysis has been evaluated for the different radioligands ⁶⁸Ga-DOTATOC, ⁶⁸Ga-DOTANOC and ¹⁸F-SiTATE. Only patients presenting with an HbA_1c in the physiological range (4.0-6.0%) at the time point of the SSTR PET/CT were included.

Results: Correlation analysis showed a significant correlation between HbA_1c and SUV_max (r=-0.542; r²= 0.293; p<0.0001) and SUVmean (r=-0.393; r²=0.154; p=0.01) using ⁶⁸Ga-DOTATOC (42 PET/CTs). In the ¹⁸F-SiTATE PET (24 PET/CTs) no significant correlation between the respective HbA_1c and SUV_max (r=-0.259; r²=0.067; p=0.222) and SUV_mean (r=-0.095; r²=0.009; p=0.658) was demonstrated. ⁶⁸Ga-DOTANOC (5 PET/CTs) as radioligand did also not show a significant correlation between HbA_1c and SUV_max (r=-0.264; r²=0.069; p=0.667) and SUV_mean (r=0.105; r²=0.011; p=0.867).

Conclusions: In contrast to other radioligands, pancreatic ⁶⁸Ga-DOTATOC uptake on PET/CT correlated moderately with the HbA_1c in patients without pancreatic diseases. Therefore, it may potentially be suitable as a predictive marker for early risk stratification in patients with pancreas-related glucose metabolism disorders. As a next step, it must be investigated how the tracer uptake varies in different pancreas related diseases to determine its value as a novel biomarker for pancreatic function.