Noninvasive quantitative evaluation of viable islet grafts using 111In‐exendin‐4 SPECT/CT

Abstract

AbstractIslet transplantation (IT) is an effective β‐cell replacement therapy for patients with type 1 diabetes; however, the lack of methods to detect islet grafts and evaluate their β‐cell mass (BCM) has limited the further optimization of IT protocols. Therefore, the development of noninvasive β‐cell imaging is required. In this study, we investigated the utility of the 111Indium‐labeled exendin‐4 probe {[Lys12(111In‐BnDTPA‐Ahx)] exendin‐4} (111In exendin‐4) to evaluate islet graft BCM after intraportal IT. The probe was cultured with various numbers of isolated islets. Streptozotocin‐induced diabetic mice were intraportally transplanted with 150 or 400 syngeneic islets. After a 6‐week observation following IT, the ex‐vivo liver graft uptake of 111In‐exendin‐4 was compared with the liver insulin content. In addition, the in‐vivo liver graft uptake of 111In exendin‐4 using SPECT/CT was compared with that of liver graft BCM measured by a histological method. As a result, probe accumulation was significantly correlated with islet numbers. The ex‐vivo liver graft uptake in the 400‐islet‐transplanted group was significantly higher than that in the control and the 150‐islet‐transplanted groups, consistent with glycemic control and liver insulin content. In conclusion, in‐vivo SPECT/CT displayed liver islet grafts, and uptakes were corroborated by histological liver BCM. 111In‐exendin‐4 SPECT/CT can be used to visualize and evaluate liver islet grafts noninvasively after intraportal IT.