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
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2024 AugAllogeneic 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.
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
PMID: 38432328
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