Sheryl Roberts, Eshita Khera, Crystal Choi, Tejas Navaratna, Jan Grimm, Greg M. Thurber and Thomas Reiner*

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 (E4_x12-Cy7) 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 (IC₅₀ = 4.6 ± 0.8 nM). Using the multi-spectral optoacoustic tomography (MSOT), we imaged E4_x12-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.