RT Journal Article
SR Electronic
T1 Optoacoustic imaging of GLP-1 Receptor with a near-infrared exendin-4 analog
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.29.068619
DO 10.1101/2020.04.29.068619
A1 Sheryl Roberts
A1 Eshita Khera
A1 Crystal Choi
A1 Tejas Navaratna
A1 Jan Grimm
A1 Greg M. Thurber
A1 Thomas Reiner
YR 2020
UL http://biorxiv.org/content/early/2020/04/30/2020.04.29.068619.abstract
AB 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 (E4x12-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 E4x12-Cy7 has a high binding affinity (IC50 = 4.6 ± 0.8 nM). Using the multi-spectral optoacoustic tomography (MSOT), we imaged E4x12-Cy7 and optoacoustically visualized ß-cell insulinoma xenografts in vivo for the first time. In the future, similar optoacoustic tracers that are specific for ß-cells and combines optoacoustic and fluorescence imaging modalities could prove to be important tools for monitoring the pancreas for the progression of diabetes.Competing Interest StatementT.R. is a shareholder of Summit Biomedical Imaging, LLC. J.G. and T.R. are co-inventors on filed U.S. patent (US20190275179A1) which covers optoacoustic imaging agents. T.R. is co-inventor on U.S. patent (WO2012121746A2), covering the composition of matter for islet imaging agents. T.R. is a paid consultant for and has received grant support from Theragnostics, Inc. This arrangement has been reviewed and approved by Memorial Sloan Kettering Cancer Center in accordance with its conflict of interest policies.