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Updated: May 15, 2026
Longitudinal In Vivo Imaging and Quantification of Human Pancreatic Islet Grafting and Contributing Host Cells in the Anterior Eye Chamber
Published on: June 11, 2020
Development and evaluation of 18F-TTCO-Cys40-Exendin-4: a PET probe for imaging transplanted islets
Zhanhong Wu1, Shuanglong Liu, Matthew Hassink
1Department of Diabetes, Endocrinology, and Metabolism, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
Unlabelled:
Because islet transplantation has become a promising treatment option for patients with type 1 diabetes, a noninvasive imaging method is greatly needed to monitor these islets over time. Here, we developed an (18)F-labeled exendin-4 in high specific activity for islet imaging by targeting the glucagonlike peptide-1 receptor (GLP-1R).
Methods:
Tetrazine ligation was used to radiolabel exendin-4 with (18)F. The receptor binding of (19/18)F-tetrazine trans-cyclooctene (TTCO)-Cys(40)-exendin-4 was evaluated in vitro with INS-1 cell and in vivo on INS-1 tumor (GLP-1R positive) and islet transplantation models.
Results:
(18)F-TTCO-Cys(40)-exendin-4 was obtained in high specific activity and could specifically bind to GLP-1R in vitro and in vivo. Unlike the radiometal-labeled exendin-4, (18)F-TTCO-Cys(40)-exendin-4 has much lower kidney uptake. (18)F-TTCO-Cys(40)-exendin-4 demonstrated its great potential for transplanted islet imaging: the liver uptake value derived from small-animal PET images correlated well with the transplanted β-cell mass determined by immunostaining. Autoradiography showed that the localizations of radioactive signal indeed corresponded to the distribution of islet grafts in the liver of islet-transplanted mice.
Conclusion:
(18)F-TTCO-Cys(40)-exendin-4 demonstrated specific binding to GLP-1R. This PET probe provides a method to noninvasively image intraportally transplanted islets.
