[原创]活体动物生物发光成像技术在新药临床前研究中的应用

Xenogen light producing animal models can be used to model disease pathways, providing researchers with information on where a drug affects a particular pathway. Armed with this information, researchers will be able to better understand the mechanism of action of a drug, expanding the potential for discovering novel therapeutic approaches. Furthermore, compound testing in these same models provides immediate data concerning bioavailability of the compound to the target tissue. Light producing animal models expand the applications for in vivo real-time imaging to include toxicology testing for both the pharmaceutical and chemical manufacturing industries.fficeffice" />

In addition to utility in drug development and toxicology, light producing animal models can be used to further validate novel gene targets discovered through genomics. Induction of the luciferase reporter in a light producing animal model in response to a disease condition or a drug treatment, may provide critical information about the role of that gene in a disease pathway.

This innovative approach provides Xenogen with the "next generation" of highly predictive models that will expand the use of in vivo biophotonic imaging across multiple therapeutic areas and functional applications in drug discovery and preclinical development.

Current LPTA Animal Models 

Xenogen LPTA?animal models are available for use in multiple therapeutic areas and development activities:

·         Drug Metabolism/Toxicology

·         Inflammation

·         Chemical Toxicity

·         Angiogenesis/Oncology

·         Endocrine Signaling

·         Metabolic Disease

·         Organ Transplant

Oncology

Xenogen applications in oncology through light producing cell lines used in conjunction with IVIS Imaging Systems offer unique opportunities to measure tumor growth and metastasis in a variety of models. in vivo bioluminescent imaging allows the non-invasive detection and quantification of orthotopic, metastatic, and spontaneous tumors in the whole mouse. Xenogen's biophotonic imaging technology has been optimized for high sensitivity, such that micrometastases can be detected that would otherwise require histopathology to identify. Xenogen oncology models can be used to assess anti-cancer therapies over the course of treatment in vivo.

·         Quantify tumor burden in the whole mouse

·         Detect micrometastases non-invasively in living animals with high sensitivity

·         Visualize metastases spontaneously generated from a primary tumor

·         Follow responses to therapeutic treatments non-invasively in longitudinal studies

Breast, Lung, and Colon Carcinoma Models

Xenogen light producing cell line models can be used to establish orthotopic mammary gland tumors, experimental lung metastasis by intravenous injection or spontaneous metastasis from a primary tumor site, or establish subcutaneous or metastatic tumor models.

Signal Transduction/Mechanism-Based Reporters

Xenogen light producing cell line models are also available that link luciferase expression to signal transduction pathways that are key to the oncogenic process. These models offer the ability to track activation of factors that signal cell death or survival, or angiogenesis.

Human Model

Angiogenic signaling can be imaged using the hVEGF1-luc/PC-3M light producing cell line.

Infectious Disease

Xenogen has developed a wide range of bioluminescent pathogenic bacteria (both Gram-positive and Gram-negative) and a number of bioluminescent fungal strains that can be used for drug discovery both in vitro and in vivo when used with Xenogen biophotonic imaging technology.

Advantages of using bioluminescent light producing microorganisms for drug discovery in vitro.

·         Rapid and readily amenable to high throughput screening, e.g., 96 or 384-well format

·         Sensitive - subtle changes in cellular viability are rapidly detected

·         Inexpensive - no additional substrates needed for bacterial assays

Xenogen's bioluminescent infectious disease light producing microorganisms have been developed to mimic both acute and chronic standard infection protocols presently used by the pharmaceutical industry, e.g., lung, sepsis, meningitis, GI, and biofilm infections. When used with a Xenogen IVIS?Imaging System, models using light producing microorganisms allow the course of an infection to be monitored as the bacteria expand and migrate to different tissues in the animal, simply by imaging the bioluminescent signal detected from infection sites within the animal. Anti-infective drugs may then be used to treat the infections and their effectiveness can be determined by the change in the bioluminescent signal.

Advantages of using light producing microorganisms for drug discovery in vivo.

·         Rapid identification of lead drug candidates

·         Real-time efficacy data

·         May help to decrease drug failure by allowing disease relapse to be monitored in the same animal

Biofilm Models Using Xenogen Light Producing Microorganisms

Xenogen has developed a rapid, continuous method for in vivo real-time monitoring of biofilms, through non-invasive imaging of bioluminescent bacteria. Xenogen light producing microorganism strains constitutively produce light without the need for stimulation or excitation, making viable cells easily detectable, allowing:

·         Quantitative monitoring of in vivo biofilms

·         Rapid and user-friendly results, that may help to accelerate drug development in vivo

·         More predictive data

Biofilm development and response to therapy can be studied effectively to follow disease progression for weeks within the same animal. The models allow examination of efficacy or relapse and resistance development to therapeutic agents.

Xenogen's biophotonic imaging technology and biofilm-forming pathogens engineered to express light offer an integrated platform for studying chronic biofilm infection, pathogen burden and metabolic activity of biofilms, non-destructively and directly on a support matrix. The model is useful for the study of pathogenesis and in vivo efficacy of therapeutic agents against both Gram-positive and Gram-negative bacterial pathogens in real time. The imaging procedure can be repeatedly performed, thereby reducing the overall number of animals used, allowing each animal to act as its own control over time, overcoming the problem of animal-to-animal variations.

Biological Support Center

Xenogen maintains a biological support center in Alameda, California. Because research takes place around the clock, a staff of scientific and technical advisors is available from 9:00 am to 5:00 pm Pacific Time to answer even the most complex questions concerning Xenogen VivoVision Systems and services. Our goal is to help you conduct the most effective and efficient research projects possible, from drug discovery through preclinical research.