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 ME; SALVETTI NR; ORTEGA HH

Salta

Congreso; LV Annual SAIB Meeting and XIV PABMB; 2019

SAIB

The most recent techniques available for real-time invivo imaging of the distribution of drugs and their metabolism in the bodyprovide a unique, early opportunity to identify which drugs will fail in thelater stages of drug development, thereby improving the quality of themolecules ultimately selected to move forward. This cutting-edge research areais so important that new equipment and technologies are presented day by day.This technology allows the visualization, characterization, and measurement ofbiological processes in living systems. In the past decade, it has beenincreasingly recognized as an important preclinical and clinical research toolthat 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 toolto improve the efficiency of the development process of new drugs and allowreducing the number of animals required in longitudinal studies as well asincreasing the data obtained from each animal. Here we present two examples ofthe use of this technology in preclinical trials, developed under an ISO 9001certified Quality Management System in accordance with the principles of GoodLaboratory Practices (BPL-OECD recognized facility). Trials were designed andexecuted using a Small Animals Imaging System (Pearl Trilogy, Licor) thatallowed analyzing in real time the distribution of the drug in  BALB/cCmedc mice. The biodistribution ofnanoparticles administered intravenously was observed by loading with specificflurophores in the NIR range of 700 nm and organs involved in their metabolism,accumulation and elimination could be identified (liver, gallbladder andkidneys).  It was also possible toanalyze the real-time distribution of heterologous immunoglobulins,administered intravenously, allowing to identify the target organs, eliminationtimes and exception route. For this, the immunoglobulins were labeled withfluorophores with fluorescence at 800 nm. At 0.5, 1, 2, 4, 6, 8, 12 and 24 hafter inoculation images were acquired. After in vivo imaging, animals weresacrificed. 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 signalwas determined by digital analysis of the images. We can conclude that in vivo imagingtechniques are extremely useful for longitudinal evaluation in pharmacodynamicstudies. Also, the intensity and location of the bioluminescent signal canprovide information about the distribution of specific molecules in animalsreducing the number of animals to be used in pharmacokinetic and pharmacodynamictests, added to the fact that their high sensitivity facilitates the adequateidentification of end-points and white organs in development of new molecules.