PT  - JOURNAL ARTICLE
AU  - Zhanhong Wu
AU  - Shuanglong Liu
AU  - Matthew Hassink
AU  - Indu Nair
AU  - Ryan Park
AU  - Lin Li
AU  - Ivan Todorov
AU  - Joseph M. Fox
AU  - Zibo Li
AU  - John E. Shively
AU  - Peter S. Conti
AU  - Fouad Kandeel
TI  - Development and Evaluation of <sup>18</sup>F-TTCO-Cys<sup>40</sup>-Exendin-4: A PET Probe for Imaging Transplanted Islets
AID  - 10.2967/jnumed.112.109694
DP  - 2013 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 244--251
VI  - 54
IP  - 2
4099  - http://jnm.snmjournals.org/content/54/2/244.short
4100  - http://jnm.snmjournals.org/content/54/2/244.full
SO  - J Nucl Med2013 Feb 01; 54
AB  - 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.