Optoacoustic imaging of GLP-1 Receptor with a near-infrared exendin-4 analog

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 (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 multispectral 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.

Emerging contrast agents for multispectral optoacoustic imaging and their biomedical applications

“…To date, a number of new biomedical applications have been achieved by using MCAs. [30][31][32][33][34][35] Pharmacokinetics is an important parameter used to study the movement of foreign substances (mostly the drugs) into, through and out of the organism, which includes the processes of liberation, absorption, distribution, metabolization and excretion. Recently, Xiao et al utilized MSOT to investigate the pharmacokinetics of HypoxiSense 680 (HS680), a commercially available and tumor-targeted MCA, in a mouse xenograft model of breast cancer (Fig.…”

“…This strategy may provide a new approach for monitoring diabetes and its progression. 34 Moreover, Kim et al designed a molecular dye named TiNIR for detection of tumor initiating cells (TIC) in human lung tumors through MSOT/fluorescence imaging. 35 Despite recent promising progresses, MCAs also exhibit some disadvantages, such as lower molar extinction coefficients, being prone to photobleaching and tendency to aggregate in aqueous media.…”