A portable multi-parametric optical spectroscopy device for key vascular and metabolic endpoints monitoring in small animals

Altered vascularity and deregulated metabolism are two important cancer hallmarksInterest in therapeutically exploiting these functional endpoints continues to growsince metabolism and vasculature significantly impact a tumor s fateThere is growing demand for systems level technologies that measure tumor metabolism within an intact microenvironment to inform strategies to prevent resistancerecurrence and metastasesVascular oxygen saturationSOand total hemoglobin concentrationTHbwithin the tumor microenvironment influence metabolism by affecting substrate availabilityby the same tokenthe nature of metabolism affects these vascular parameters by affecting substrate demandConsidering the importance of metabolism and vascularity to cancer biology there are surprisingly few techniques available to provide a systems level approach to measure metabolism and the associated vasculature in vivoThere is a significant unmet preclinical need for simultaneous measurement of vascularity and metabolism of tumors in vivo for pharmacology researchOur group has proposed a plan to developvalidateand commercialize a portableadjunct optical spectroscopy device that can quantitatively measure vascular and metabolic endpoints including oxygen saturationtotal hemoglobin concentrationglucose uptake and mitochondrial membrane potential in tumors in vivoZenalux Biomedical has previously demonstrated that quantitative diffuse reflectance spectroscopyZenascopeTMcan be used to assess relevant vascular endpoints in a variety of cancersIndependentlythe Ramanujam lab has demonstrated with both in vivo microscopy of animal models and in vivo fluorescence spectroscopy of phantoms the ability to simultaneously measure key endpoints of metabolism using the fluorophoresNBDGglucose uptakeand TMREmitochondrial membrane potentialWe have detailed a plan in this Phase I STTR proposal to extend the capability of our existing Zenascopeto a multiparametric spectroscopy system capable of providing accurate and precise analysis of metabolism and functional vascular endpoints of solid tumors in small animalsThe performance of the portable ZenascopeZFsystem will be optimized against the gold standard research grade system using tissue mimicking fluorescence phantomsThe simultaneous capture ofNBDG and TMRE will be optimized and extensively validated in vivo inTTandNR murine breast cancer tumors using the proposed ZenascopeZFsystemFurther the ZenascopeZFmeasured optical endpoints will be validated against metabolic features independently measured by wellestablished laboratory techniquesSeahorse Assay and MetabolomicsThe primary deliverables will bea portable spectroscopy platformZenascopeZFthat is able to simultaneously capture multiple vascular and metabolic endpointsandan optimized and validated protocol for simultaneous spectroscopy of glucose uptake and mitochondrial oxidative phosphorylation in solid tumors in vivoThe resulting ZFwill fill the critical need for systems level tools to measure cancer metabolism in small animal modelsand will enable investigations ranging from fundamental studies of cancer signaling pathways to clinical patient derived xenograft studies to test targeted agents for personalized therapy The goal of our proposed program is to establish a portableoptical productZenascopethat can provide accurate and precise analysis of the glucose uptakemitochondrial membrane potentialand functional vascular endpoints of solid tumors in small animalsThe capability to augment our technology to target tumor metabolism allows us to create a product that has distinct capabilities to measure tumor bioenergetics that no other spectroscopy system on the market providesThe resulting Zenascopewill be well suited for systems level investigation of metabolism in small animal tumor modelsthereby enabling the development of new strategies to overcome treatment resistance and poor outcomes in breast cancer