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, [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 (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. [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 type 1 diabetes.

中文翻译：

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遗传性糖尿病猪门脉内新生猪胰岛移植物的功能成熟和纵向成像

同种异体门静脉内胰岛移植 (ITx) 已成为治疗控制不佳的 1 型糖尿病患者的既定治疗方法。然而，移植后存活的β细胞量的损失仍然是一个重大挑战。因此，需要用于长期监测移植命运的无创成像方法。在这项研究中，使用[Ga]Ga-DOTA-exendin-4正电子发射断层扫描/计算机断层扫描（PET/CT）对异体新生猪胰岛（NPI）进行门静脉内移植到免疫抑制的遗传性糖尿病猪体内后进行重复监测。 NPI 移植（每公斤体重 3320-15,000 胰岛当量）导致对外源性胰岛素治疗的需求减少，并最终在 5 至 10 周后四分之三的动物的血糖水平恢复正常。纵向 PET/CT 测量显示移植肝脏中的标准摄取值显着增加。组织学分析证实移植肝脏中存在移植良好的成熟胰岛簇。我们的研究提出了一种用于同种异体门静脉内 ITx 的新型大型动物模型。相对较小剂量的 NPI 足以使临床相关糖尿病猪模型的血糖水平正常化。 [Ga]Ga-DOTA-exendin-4 PET/CT 被证明对于胰岛移植的纵向监测是有效的。因此，它可以在优化 ITx 作为 1 型糖尿病的治疗方法方面发挥至关重要的作用。