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

Abstract

Islet 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.