In Vivo Visualization of β-Cells by Targeting of GPR44

Diabetes. 2018 Feb;67(2):182-192. doi: 10.2337/db17-0764. Epub 2017 Dec 5.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Biomarkers / metabolism
  • Biopsy
  • Carbon Radioisotopes
  • Diabetes Mellitus, Type 1 / diagnostic imaging*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 2 / diagnostic imaging*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Intestinal Elimination
  • Islets of Langerhans / diagnostic imaging*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Islets of Langerhans Transplantation / diagnostic imaging
  • Islets of Langerhans Transplantation / pathology
  • Ligands
  • Macaca fascicularis
  • Magnetic Resonance Imaging
  • Mice, Nude
  • Phenyl Ethers / administration & dosage
  • Phenyl Ethers / pharmacokinetics*
  • Positron Emission Tomography Computed Tomography
  • Proof of Concept Study
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / metabolism*
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / metabolism*
  • Sus scrofa
  • Tissue Distribution
  • Transplantation, Heterologous
  • Transplantation, Heterotopic


  • Biomarkers
  • Carbon Radioisotopes
  • Ligands
  • Phenyl Ethers
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor