%0 Journal Article
%A Zhanhong Wu
%A Shuanglong Liu
%A Matthew Hassink
%A Indu Nair
%A Ryan Park
%A Lin Li
%A Ivan Todorov
%A Joseph M. Fox
%A Zibo Li
%A John E. Shively
%A Peter S. Conti
%A Fouad Kandeel
%T Development and Evaluation of 18F-TTCO-Cys40-Exendin-4: A PET Probe for Imaging Transplanted Islets
%D 2013
%R 10.2967/jnumed.112.109694
%J Journal of Nuclear Medicine
%P 244-251
%V 54
%N 2
%X 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 18F-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 18F. The receptor binding of 19/18F-tetrazine trans-cyclooctene (TTCO)-Cys40-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: 18F-TTCO-Cys40-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, 18F-TTCO-Cys40-exendin-4 has much lower kidney uptake. 18F-TTCO-Cys40-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: 18F-TTCO-Cys40-exendin-4 demonstrated specific binding to GLP-1R. This PET probe provides a method to noninvasively image intraportally transplanted islets.
%U https://jnm.snmjournals.org/content/jnumed/54/2/244.full.pdf