Imaging Hepatocellular Liver Injury using NIR-labeled Annexin V

Drug induced liver injury (DILI) is a major reason for late stage termination of drug discovery research projects, highlighting the importance of early integration of liver safety assessment in the drug development process. A technical approach for in vivo toxicology determination was developed using Acetaminophen (APAP), a commonly used over-the-counter analgesic and antipyretic drug, to induce acute hepatocellular liver injury. PerkinElmer imaging technology and near infrared (NIR) labeled Annexin V (Annexin-VivoTM 750) were used to detect and quantify and necrosis associated with this type of liver toxicity. Both fluorescent tomographic imaging (FMT® 4000 and IVIS® SpectrumCT), and higher throughput epifluorescence imaging (IVIS SpectrumCT), provided excellent detection of Annexin-Vivo fluorescence in the liver. Histology and plasma alanine transaminase (ALT) confirmed the kinetics of tissue necrosis, and more extensive liver damage was seen but with an apparent decrease in tissue PS and plasma ALT by 48 hours, suggesting a decline in the induction of tissue destruction. Compared to conventional plasma/serum assays, in vivo imaging can offer fast, quantitative imaging results directly assessing the tissue of interest. Imaging Hepatocellular Liver Injury using NIR-labeled Annexin V A P P L I C A T I O N N O T E Pre-clinical in vivo Imaging Authors: Kristine O. Vasquez Jeffrey D. Peterson, Ph.D. PerkinElmer, Inc. Hopkinton, MA