A Quantitative Optical Sensor to Monitor Pre-Clinical Tumor Vascular Physiology

DESCRIPTION (provided by applicant): Angiogenesis and hypoxia can significantly influence the efficacy of therapy and the behavior of surviving tumor cells. This important fact is supported by a vast amount of literature on pre-clinical models and clinical studies. There is growing demand for technologies to measure tumor hypoxia and angiogenesis temporally and spatially in vivo to enable advances in drug screening, development and optimization. This is particularly useful in the emerging era of anti-angiogenesis and anti-hypoxia therapies. We propose to develop a portable, low power consumption and low-cost, yet accurate and reliable, multimodality optical spectroscopy system with a novel fiber-optic probe to dynamically characterize tumor hypoxia, angiogenesis, and metabolism as well as tissue drug concentration in small animal models without operator bias. The multimodality optical spectroscopy system will be a laptop or battery powered console with the integration of multiple LEDs, a dual-channel spectrometer, a fiber optic probe, electronics and custom software that can be used to perform both diffuse reflectance and fluorescence spectroscopy in vivo. The fiber-optic probe will include an interferometric pressure sensor that can be used to control the probe-tissue pressure for reliable and reproducible spectroscopic measurement of tissue optical properties. The aims of the proposed work (Phase I) will be to (1) design the core technology using LEDs and an interferometric fiber-optic sensor, (2) characterize its performance metrics and (3) validate its utility in a pre-clinical mammary tumor model. This technology will be extended to include quantitative fluorescence measurements in the Phase II STTR project period along with different probe designs to provide flexibility in implementation of this technology to ectopic (tumors grown on flank) and orthotopic models. The commercial device can be marketed as either a single- modality (diffuse reflectance) or a multi-modality (reflectance and fluorescence) device. The outcome of Phase I will lead to a 1st generation Quantilux device which can be productized while the multi-modality 2nd generation device is being refined.The overall objective in Phase II and beyond will be to develop a marketable version of the device and validate its utility for longitudinal tumor therapy monitoring in mouse tumor models. PUBLIC HEALTH RELEVANCE: Our long-term goal is to develop and commercialize a compact, low power consumption, low-cost, yet accurate and reliable, optical spectroscopy system, to dynamically and non-destructively quantify tumor physiological and morphological endpoints such as angiogenesis and hypoxia in small animal models. This proposal is significantly relevant to public health because angiogenesis andhypoxia can significantly influence the efficacy of therapy and the behavior of surviving tumor cells.