Monitoring beta cell survival after intrahepatic islet transplantation using dynamic exendin PET imaging: a proof-of-concept study in individuals with type 1 diabetes

Intrahepatic transplantation of islets of Langerhans (ITx) is a treatment option for individuals with complicated type 1 diabetes and profoundly unstable glycemic control, but its therapeutic success is hampered by deterioration of graft function over time. To improve ITx strategies, technologies to non-invasively monitor the fate and survival of transplanted islets over time, are of great potential value. We used [⁶⁸Ga]Ga-NODAGA-exendin-4 (⁶⁸Ga-exendin) positron emission tomography/computed tomography (PET/CT) imaging to demonstrate the feasibility to quantify beta cell mass in intrahepatic islet grafts in 13 individuals with type 1 diabetes, 9 after ITx with functional islet grafts and 4 non-transplanted controls. Beta cell function was measured by mixed-meal tolerance test. With dynamic ⁶⁸Ga-exendin PET/CT images, we determined tracer accumulation in hepatic hotspots, and intrahepatic fat was assessed using magnetic resonance imaging and spectroscopy. Quantification of hepatic hotspots showed a significantly higher uptake of ⁶⁸Ga-exendin in the ITx group compared to controls (0.55 [0.51-0.63] vs. 0.43 [0.42-0.45]). GLP-1 receptor expression was found in transplanted islets by immunohistochemistry. Intrahepatic fat was not detected in the majority of the individuals. Our study provides the first clinical evidence that radiolabeled exendin imaging can be used to monitor viable transplanted islets after intraportal ITx.

(ClinicalTrials.gov number: NCT03785236)