Please use this identifier to cite or link to this item:
|Title:||In vivo visualization of β-cells by targeting of GPR44||Authors:||Eriksson, Olof
Selvaraju, Ram K.
Winzell, Maria Sörhede
|Keywords:||Science::Medicine||Issue Date:||2018||Source:||Eriksson, O., Johnström, P., Cselenyi, Z., Jahan, M., Selvaraju, R. K., Jensen-Waern, M., . . . Korsgren, O. (2018). In vivo visualization of β-cells by targeting of GPR44. Diabetes, 67(2), 182-192. doi:10.2337/db17-0764||Journal:||Diabetes||Abstract:||GPR44 expression has recently been described as highly β-cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes. A radiolabeled small-molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of β-cells in pigs and nonhuman primates by positron emission tomography as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from subjects without and with diabetes, in combination with insulin staining, was performed to assess β-cell selectivity of the radiotracer. Proof of principle of in vivo targeting of human islets by [11C]AZ12204657 was shown in the immunodeficient mouse transplantation model. Furthermore, [11C]AZ12204657 bound by a GPR44-mediated mechanism in pancreatic sections from humans and pigs without diabetes, but not those with diabetes. In vivo [11C]AZ12204657 bound specifically to GPR44 in pancreas and spleen and could be competed away dose-dependently in nondiabetic pigs and nonhuman primates. [11C]AZ12204657 is a first-in-class surrogate imaging biomarker for pancreatic β-cells by targeting the protein GPR44.||URI:||https://hdl.handle.net/10356/142005||ISSN:||0012-1797||DOI:||10.2337/db17-0764||Rights:||© 2017 American Diabetes Association. All rights reserved.||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
Updated on Feb 1, 2023
Web of ScienceTM
Updated on Feb 2, 2023
Updated on Feb 6, 2023
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.