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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.
Epifluorescence (2D) imaging of superficially implanted mouse tumor xenograft models offers a fast and simple method for assessing tumor progression or response to therapy. This approach for tumor assessment requires the use of near infrared (NIR) imaging agents specific for different aspects of tumor biology, and this Application Note highlights the ease and utility of multiplex NIR fluorescence imaging to characterize the complex biology within tumors growing in a living mouse.
Optical-based in vivo imaging of vascular changes and vascular leak is an emerging modality for studying altered physiology in a variety of different cancers and inflammatory states. A number of fluorescent imaging probes that circulate with the blood, but have no target selectivity, have been used to detect tumor leakiness as an indication of abnormal tumor vasculature. Inflammation is also characterized by distinct vascular changes, including vasodilation and increased vascular permeability, which are induced by the actions of various inflammatory mediators. This process is essential for facilitating access for appropriate cells, cytokines, and other factors to tissue sites in need of healing or protection from infection. This application note investigates the use of three fluorescent imaging probes, to detect and monitor vascular leak and inflammation in preclinical mouse breast cancer models.
Fluorescent dyes have been used for many years to label cells for microscopy studies, and a variety of dyes in the visible fluorescence spectrum are available to label different cellular compartments and organelles. Efficient delivery of the fluorophore to the cell without excessively modifying surface proteins or perturbing cell function is the major biotechnological challenge. In addition, researchers have taken on the challenge of in vivo imaging, focusing on near infrared (NIR) dyes that fluoresce in a spectral region better suited for in vivo imaging due to reduced background and higher tissue penetration.
Cancer chemotherapy can produce severe side effects such as suppression of immune function and damage to heart muscle, gastrointestinal tract, and liver. If serious enough, tissue injury can be a major reason for late stage termination of drug discovery research projects, so it is becoming more important to integrate safety/toxicology assessments earlier in the drug development process. There are a variety of traditional serum markers, tailored mechanistically to specific tissues, however there are no current non-invasive assessment tools that are capable of looking broadly at in situ biological changes in target and non-target tissue induced by chemical insult.
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