title: Development and evaluation of 18F-TTCO-Cys40-Exendin-4: a PET probe for imaging transplanted islets.
abstract: 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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Department of Diabetes, Endocrinology, and Metabolism, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Zhanhong
authors.initials: Z
authors.lastname: Wu
authors.forename: Shuanglong
authors.initials: S
authors.lastname: Liu
authors.forename: Matthew
authors.initials: M
authors.lastname: Hassink
authors.forename: Indu
authors.initials: I
authors.lastname: Nair
authors.forename: Ryan
authors.initials: R
authors.lastname: Park
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Ivan
authors.initials: I
authors.lastname: Todorov
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Fox
authors.forename: Zibo
authors.initials: Z
authors.lastname: Li
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
authors.forename: Fouad
authors.initials: F
authors.lastname: Kandeel
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D034242:Cyclooctanes; D003952:Diagnostic Imaging / Q000379:methods*; D000077270:Exenatide; D005462:Fluorine Radioisotopes; D005786:Gene Expression Regulation; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology; D007340:Insulinoma / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009683:Nuclear Medicine / Q000379:methods*; D010455:Peptides; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism; D014688:Venoms
chemical_list: D034242:Cyclooctanes; D005462:Fluorine Radioisotopes; C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide