Facilitating the development of novel therapeutic strategies via in vivo optical imaging techniques

Abstract

The BioLISYS Laboratory at CUT is developing novel fluorescence-based techniques for in vivo imaging of small animals with applications in cardiovascular and cancer therapeutics. These include the development of an in vivo flow cytometer in order to monitor fluorescently labeled cells in circulation as well as a whole body reflectance imaging system for detection of fluorescence and bioluminescence signal from cells and tissues in murine models of disease. The in vivo flow cytometer has been designed as a minimally invasive optical tool for the real time detection/quantification of fluorescent cells in circulation of living animals without the need to sequentially extract blood samples or sacrifice animals. Thus the system allows for the continuous monitoring of a cell population of interest over long time periods in order to assess dynamic changes in circulation. The optical reflectance imaging system combines fluorescence and bioluminescence imaging capabilities with a large field of view in order to enable imaging over a wide area of the animal. The noninvasive, quantitative method enables longitudinal studies of physiological changes in disease and allows for continuous monitoring in the same mouse over an extended time period, in order to evaluate biodistribution and therapeutic response of experimental therapeutic agents. The imaging systems have been employed in the in vivo analysis of cardiovascular implants and novel biomaterials in order to evaluate the inflammatory response of vascular tissue to stent implantation and stent biocorrosion via the in vivo monitoring of the degree of inflammation, macrophage infiltration and cytokine expression in tissue surrounding stents deployed in mice abdominal aortas. In cancer therapeutics, the in vivo imaging systems have been used to develop a novel therapeutic system for targeted miRNA delivery to tumors, via microparticles that are derived from mesenchymal stem cells. Fluorescently labeled miRNA-loaded microparticles injected into the tail vein of tumor bearing mouse were monitored in circulation via the in vivo flow cytometer while their biodistribution and targeting specificity was detected in tumor sites via the fluorescence based whole body reflectance imaging system. Furthermore, tumor progression and therapeutic response to miRNA therapy delivered via local and systemic administration of the MSC-derived microparticles was monitored in real time via the imaging of fluorescence and bioluminescence expressing tumors by whole body reflectance imaging.