SignificanceEmerging evidence that aggressive breast tumors rely on various substrates including lipids and glucose to proliferate and recur necessitates the development of tools to track multiple metabolic and vascular endpoints concurrently in vivo.AimOur quantitative spectroscopy technique provides time-matched measurements of the three major axes of breast cancer metabolism as well as tissue vascular properties in vivo.ApproachWe leverage exogenous fluorophores to quantify oxidative phosphorylation, glucose uptake, and fatty acid oxidation, and endogenous contrast for measurements of hemoglobin and oxygen saturation. An inverse Monte Carlo algorithm corrects for aberrations resulting from tissue optical properties, allowing the unmixing of spectrally overlapping fluorophores.ResultsImplementation of our inverse Monte Carlo resulted in a linear relationship of fluorophore intensity with concentration (R2<0.99) in tissue-mimicking phantom validation studies. We next sequenced fluorophore delivery to faithfully recapitulate independent measurement of each fluorophore. The ratio of Bodipy FL C16/2-NBDG administered to a single animal is not different from that in paired animals receiving individual fluorophores (p=n.s.). Clustering of five variables was effective in distinguishing tumor from mammary tissue (sensitivity = 0.75, specificity = 0.83, and accuracy = 0.79).ConclusionsOur system can measure major axes of metabolism and associated vascular endpoints, allowing for future study of tumor metabolic flexibility.
We developed an approach to quantify intra-tumoral metabolic heterogeneity of in vivo tumor models by leveraging a computationally designed multi-scale microscope and a suite of exogenous fluorescent contrast agents to provide functional and structural information.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.