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Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes. However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, noninvasive imaging methods for long-term monitoring of the transplant fate are required. In this study, [68Ga]Ga-DOTA-exendin-4 positron emission tomography/computed tomography (PET/CT) was used for repeated monitoring of allogeneic neonatal porcine islets (NPI) after intraportal transplantation into immunosuppressed genetically diabetic pigs. NPI transplantation (3320-15,000 islet equivalents per kg body weight) led to a reduced need for exogenous insulin therapy and finally normalization of blood glucose levels in 3 out of 4 animals after 5 to 10 weeks. Longitudinal PET/CT measurements revealed a significant increase in standard uptake values in graft-bearing livers. Histologic analysis confirmed the presence of well-engrafted, mature islet clusters in the transplanted livers. Our study presents a novel large animal model for allogeneic intraportal ITx. A relatively small dose of NPIs was sufficient to normalize blood glucose levels in a clinically relevant diabetic pig model. [68Ga]Ga-DOTA-exendin-4 PET/CT proved to be efficacious for longitudinal monitoring of islet transplants. Thus, it could play a crucial role in optimizing ITx as a curative therapy for type 1 diabetes. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Johanna Pilz, Nicol Gloddek, Felix Lindheimer, Magdalena J Lindner, Daniel Puhr-Westerheide, Muzzafer Ümütlü, Clemens Cyran, Max Seidensticker, Richard Lindner, Martin Kraetzl, Simone Renner, Daphne Merkus, Daniel Teupser, Peter Bartenstein, Sibylle I Ziegler, Eckhard Wolf, Elisabeth Kemter. Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2024 Aug;24(8):1395-1405

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PMID: 38432328

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