The Development of an In Vivo Mobile Dynamic Microscopy System that Images the Hypoxic Microenvironments of Cancerous Tumors via Fluorescent and Phosphorescent Nanoparticles

Abstract

Hypoxic tumor microenvironments have a clear correlation with a lack of radiosensitivity and diminished therapy response. This relationship can be described through the use of fluorescent and phosphorescent nanoparticles optically imaged in a mouse model. Through the use of this ratiometric oxygen sensing, the hypoxic state of the cancerous tumor can be compared. Normally, the microscope imaging system requires the mouse to be imaged under anesthesia and data recorded for a short amount of time. This has led to challenges in clearly defining the oxygen saturation levels in hemoglobin because the anesthesia can affect the tumor vascular dynamics. Moreover, it is desirable to track blood flow and oxygenation changes over a longer period of time in order to characterize the dynamics of cycling hypoxia and therapeutic response. Therefore, a mobile imaging apparatus has been designed and built to directly attach to the dorsal skinfold window chamber installed on nude murine models. Current progress includes quantifiable ratiometric oxygenation in boron nanoparticle solutions imaged under UV light with the mobile unit. The concept has also been successful in in vivo studies for anesthetized mice. The mobile unit is capable of resolving vasculature and is sensitive enough to record nanoparticle emissions originating from tissue in a mouse window chamber model. This system will use dynamic microscopy to image the tumor’s hypoxic environment on un-anesthetized mice and yield insight into tumor biology and therapeutic response.