USE OF IN VIVO IMAGING SYSTEM FOR PRECLINICAL EVALUATION: EXAMPLES OF ITS APPLICATION IN DRUG DEVELOPMENT

SALINAS F; BERENGENO A; SANTIAGO G; MARELLI B; BARAVALLE M.E; SALVETTI NR; ORTEGA H.H.

Salta

Congreso; Joint LV Annual SAIB Meeting and XIV PABMB Congress; 2019

Saib

The most recent techniques available for real-time in vivo imaging of the distribution of drugs and their metabolism in the body provide a unique, early opportunity to identify which drugs will fail in the later stages of drug development, thereby improving the quality of the molecules ultimately selected to move forward. This cutting-edge research area is so important that new equipment and technologies are presented day by day. This technology allows the visualization, characterization, and measurement of biological processes in living systems. In the past decade, it has been increasingly recognized as an important preclinical and clinical research tool that can be used to speed up the long-term engagement of the drug development process. The use of in vivo images during preclinical development is a fundamental tool to improve the efficiency of the development process of new drugs and allow reducing the number of animals required in longitudinal studies as well as increasing the data obtained from each animal. Here we present two examples of the use of this technology in preclinical trials, developed under an ISO 9001 certified Quality Management System in accordance with the principles of Good Laboratory Practices (BPL-OECD recognized facility). Trials were designed and executed using a Small Animals Imaging System (Pearl Trilogy, Licor) that allowed analyzing in real time the distribution of the drug in BALB/cCmedc mice. The biodistribution of nanoparticles administered intravenously was observed by loading with specific flurophores in the NIR range of 700 nm and organs involved in their metabolism, accumulation and elimination could be identified (liver, gallbladder and kidneys). It was also possible to analyze the real-time distribution of heterologous immunoglobulins, administered intravenously, allowing to identify the target organs, elimination times and exception route. For this, the immunoglobulins were labeled with fluorophores with fluorescence at 800 nm. At 0.5, 1, 2, 4, 6, 8, 12 and 24 h after inoculation images were acquired. After in vivo imaging, animals were sacrificed. Ex vivo imaging after removal of brain, heart, lungs, liver, spleen, kidneys, stomach, intestines, adrenal glands, eyes, seminal vesicles, prostate and bladder was performed. The intensity and location of the signal was determined by digital analysis of the images. We can conclude that in vivo imaging techniques are extremely useful for longitudinal evaluation in pharmacodynamic studies. Also, the intensity and location of the bioluminescent signal can provide information about the distribution of specific molecules in animals reducing the number of animals to be used in pharmacokinetic and pharmacodynamic tests, added to the fact that their high sensitivity facilitates the adequate identification of end-points and white organs in development of new molecules.The Center for Comparative Medicine is the unique center integrated to an institution of the Scientific-Technological System in Argentina that combines the certifications and qualifications corresponding to SENASA, ANMAT, ISO 9001 and BPL-OECD. Design and develop biological tests and preclinical trials of high complexity according to national and international standards. We are always interested in working in collaboration with other scientific groups. More information in: www.cmc.unl.edu.ar