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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.
With the potential to treat a wide range of disease, from organ damage to congenital defects, stem cell research and tissue engineering form the underlying basis of regenerative medicine. Significant advances in the science of skin regeneration, for example, have now made it possible to develop and grow artificial skin grafts in a lab for treatment of burn victims. Other therapeutic applications include the use of stem cells to treat and repair central nervous system diseases such as ischemia and cerebral palsy, cardiovascular diseases, as well as autoimmune diseases including type I diabetes.
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.
Osteoarthritis (OA) is the most common form of arthritis and affects a considerable portion of the elderly population. In the U.S., it is estimated that more than 630 million people worldwide have this chronic condition, generally in the knees. OA occurs when the cartilage that cushions the ends of bones within the joints gradually deteriorates, causing synovitis and joint deformation.
The goal of OA research is to identify new therapeutic strategies that could prevent, reduce, halt progression, or repair the existing damage to the joint. Non-invasive in vivo imaging such as microCT is the standard modality for bone research due to its ability to obtain high-resolution images at an x-ray dose low enough as not to harm the animal. This makes microCT ideal for monitoring disease progression and response to treatments in the same animal over time. However, microCT data visualization and analysis can be cumbersome and time consuming. In this application note, we compared standard microCT software and advanced bone software to investigate bone erosion in an OA rat model.
Quantitative pre-clinical fluorescence imaging transcends the boundaries of traditional optical imaging of biological structures and physiology by providing information at the molecular level about disease states and therapeutic response. Fluorescent Pre-clinical Imaging Agents and FMT® (Fluorescence Molecular Tomography) Quantitative Pre-clinical Imaging Systems represent powerful tools for research and drug development in the imaging of biological processes and pharmaceutical activity in living animals.
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.
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.
X-ray CT imaging is commonly used for skeletal imaging as bones are densely mineralized tissues with excellent x-ray attenuation properties. In contrast, soft, less dense tissues often prove to be challenging to image due to their lack of sufficient tissue density. Soft tissues such as muscle, blood vessels and internal organs share similar x-ray attenuation characteristics and are not distinguishable under typical CT settings. In order to introduce density that would improve soft tissue contrast, several contrast agents have been developed for use in clinical and preclinical settings. This application note outlines the use of iodine and nanoparticle-based contrast agents for imaging soft tissues and vasculature in various organs using the Quantum GX to gain further insights into disease and therapeutic response.
Targeted cancer therapy aims to block key signaling pathways that are critical for tumor cell growth and survival. The blockage eventually results in cell death via apoptosis and tumor growth suppression. Encouraged by the success in clinical development, many academic and pharmaceutical researcher are in active pursuit of the improvement of next generation targeted anti-cancer drugs. As a result, many new chemical and biological entities are emerging from initial screening of in vitro, in vitro and/or in silico selection processes. From the perspective of drug development, it poses a great challenge on the next stage of in vivo validation and demands a robust, accurate, and efficient method for assessment of these candidates in living animal models.
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.
Targeted cancer therapy aims to block key signaling pathways that are critical for tumor cell growth and survival. The blockage eventually results in cell death via apoptosis and eventual tumor growth suppression. This strategy has proven to be quite effective, and the FDA has approved several targeted therapeutics in the past decade. Encouraged by the success in clinical development, many academic and pharmaceutical researchers are in active pursuit of improved next generation targeted anti-cancer drugs. As a result, many new chemical and biological entities are emerging from initial screening of in vitro, in vitro and/or in silico selection processes. From the perspective of drug development, it poses a great challenge for the next stage of in vivo validation and demands a robust, accurate, and efficient method for assessment of these candidates in living animal models.
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