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Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs.
American Journal of Transplantation 2024 March 2
Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes (T1D). However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, non-invasive imaging methods for long-term monitoring of the transplant fate are required. In this study, [68 Ga]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 (3.3k-15.0k 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 5-10 weeks. Longitudinal PET/CT measurements revealed a significant increase of standard uptake values in graft bearing livers. Histological 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. [68 Ga]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 T1D.
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