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-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-Cy7 has a high-binding affinity (dissociation constant, Kd, 4.6 ± 0.8 nM). Using the multispectral optoacoustic tomography, we imaged E4-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.