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Pilz, Johanna ORCID logoORCID: https://orcid.org/0009-0007-7266-1894; Gloddek, Nicol ORCID logoORCID: https://orcid.org/0009-0001-2229-8034; Lindheimer, Felix ORCID logoORCID: https://orcid.org/0009-0002-6904-2623; Lindner, Magdalena Julia; Puhr-Westerheide, Daniel ORCID logoORCID: https://orcid.org/0000-0003-3669-5572; Ümütlü, Muzzafer; Cyran, Clemens ORCID logoORCID: https://orcid.org/0000-0001-5630-6242; Seidensticker, Max ORCID logoORCID: https://orcid.org/0000-0002-2481-5410; Lindner, Richard ORCID logoORCID: https://orcid.org/0000-0003-1836-5377; Kraetzl, Martin ORCID logoORCID: https://orcid.org/0000-0002-8449-177X; Renner, Simone ORCID logoORCID: https://orcid.org/0000-0002-5866-4577; Merkus, Daphne ORCID logoORCID: https://orcid.org/0000-0002-4852-831X; Teupser, Daniel ORCID logoORCID: https://orcid.org/0000-0001-9843-0145; Bartenstein, Peter ORCID logoORCID: https://orcid.org/0009-0005-0734-4994; Ziegler, Sibylle I. ORCID logoORCID: https://orcid.org/0000-0002-5321-4817; Wolf, Eckhard ORCID logoORCID: https://orcid.org/0000-0002-0430-9510 und Kemter, Elisabeth ORCID logoORCID: https://orcid.org/0000-0001-7785-7502 (2024): Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs. In: American Journal of Transplantation, Bd. 24, Nr. 8: S. 1395-1405 [PDF, 2MB]

Abstract

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.

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