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

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, E4(x12)-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 E4(x12)-Cy7 has a high-binding affinity (dissociation constant, Kd, 4.6 +/- 0.8 nM). Using the multispectral optoacoustic tomography, we imaged E4(x12)-Cy7 and optoacoustically visualized beta-cell insulinoma xenografts in vivo for the first time. In the future, similar optoacoustic tracers that are specific for beta-cells and combines optoacoustic and fluorescence imaging modalities could prove to be important tools for monitoring the pancreas for the progression of diabetes.

Automated summary

This study reports the development and in vivo validation testing of a broad-spectrum and high-absorbance near-infrared optoacoustic contrast agent targeting GLP-1R for imaging pancreatic islets. Future optoacoustic tracers specific for beta-cells could be important tools for monitoring the progression of diabetes in the pancreas.