In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent Academic Article uri icon


MeSH Major

  • Adenoma, Islet Cell
  • Copper Radioisotopes
  • Multimodal Imaging
  • Optical Imaging
  • Pancreas
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Receptors, Glucagon


  • Accurate visualization and quantification of β-cell mass is critical for the improved understanding, diagnosis, and treatment of both type 1 diabetes (T1D) and insulinoma. Here, we describe the synthesis of a bimodal imaging probe (PET/fluorescence) for imaging GLP-1R expression in the pancreas and in pancreatic islet cell tumors. The conjugation of a bimodal imaging tag containing a near-infrared fluorescent dye, and the copper chelator sarcophagine to the GLP-1R targeting peptide exendin-4 provided the basis for the bimodal imaging probe. Conjugation was performed via a novel sequential one-pot synthetic procedure including (64)Cu radiolabeling and copper-catalyzed click-conjugation. The bimodal imaging agent (64)Cu-E4-Fl was synthesized in good radiochemical yield and specific activity (RCY = 36%, specific activity: 141 μCi/μg, >98% radiochemical purity). The agent showed good performance in vivo and ex vivo, visualizing small xenografts (<2 mm) with PET and pancreatic β-cell mass by phosphor autoradiography. Using the fluorescent properties of the probe, we were able to detect individual pancreatic islets, confirming specific binding to GLP-1R and surpassing the sensitivity of the radioactive label. The use of bimodal PET/fluorescent imaging probes is promising for preoperative imaging and fluorescence-assisted analysis of patient tissues. We believe that our procedure could become relevant as a protocol for the development of bimodal imaging agents.

publication date

  • July 16, 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4215873

Digital Object Identifier (DOI)

  • 10.1021/bc500178d

PubMed ID

  • 24856928

Additional Document Info

start page

  • 1323

end page

  • 30


  • 25


  • 7