Optoacoustic Imaging of Glucagon-like Peptide-1 Receptor with a Near-Infrared Exendin-4 Analog

J Nucl Med. 2021 Jun 1;62(6):839-848. doi: 10.2967/jnumed.120.252262. Epub 2020 Oct 23.

Abstract

Limitations in current imaging tools have long challenged the imaging of small pancreatic islets in animal models. Here, we report the first development and in vivo validation testing of a broad-spectrum and high-absorbance near-infrared optoacoustic contrast agent, E4x12-Cy7. Our near-infrared tracer is based on the amino acid sequence of exendin-4 and targets the glucagon-like peptide-1 receptor (GLP-1R). Cell assays confirmed that E4x12-Cy7 has a high-binding affinity (dissociation constant, Kd, 4.6 ± 0.8 nM). Using the multispectral optoacoustic tomography, we imaged E4x12-Cy7 and optoacoustically visualized β-cell insulinoma xenografts in vivo for the first time. In the future, similar optoacoustic tracers that are specific for β-cells and combines optoacoustic and fluorescence imaging modalities could prove to be important tools for monitoring the pancreas for the progression of diabetes.

Keywords: MSOT; diabetes; exendin-4; near infrared; optoacoustic; sonophore; β-cell imaging.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Exenatide / chemistry*
  • Exenatide / pharmacokinetics
  • Female
  • Glucagon-Like Peptide-1 Receptor / metabolism*
  • Infrared Rays*
  • Insulinoma / metabolism
  • Insulinoma / pathology
  • Mice
  • Photoacoustic Techniques / methods*
  • Tissue Distribution

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Exenatide