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

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posted on 2023-04-17, 20:25 authored by Theodorus J.P. Jansen, Mijke Buitinga, Marti Boss, Michiel F. Nijhoff, Maarten Brom, Bastiaan E. de Galan, Marinette van der Graaf, Sebastiaan van Koeverden, Marie -Christine Vantyghem, Amandine Beron, François Pattou, Marten A. Engelse, Irina Velikyan, Olof Eriksson, Eelco J.P. de Koning, Martin Gotthardt

  

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.

Funding

This work is supported by BetaCure (FP7/2014–2018, grant agreement 602812), and Diabetes Foundation The Netherlands Fellowship (2015-81-1845). This work is also supported by IMI2-JU under grant agreement No 115797 (INNODIA) and No 948268 (INNODIA HARVEST). This joint undertaking receives support from the Union’s Horizon 2020 research and innovation program and EFPIA, JDRF and The Leona M. and Harry B. Helmsley Charitable Trust. Olof Eriksson’s position is supported by SciLifeLab and the Swedish Research Council (2020-02312).

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