Near-simultaneous quantification of glucose uptake, mitochondrial membrane potential, and vascular parameters in murine flank tumors using quantitative diffuse reflectance and fluorescence spectroscopy

Caigang Zhu; Hannah L Martin; Brian T Crouch; Amy F Martinez; Martin Li; Gregory M Palmer; Mark W Dewhirst; Nimmi Ramanujam

doi:10.1364/BOE.9.003399

Near-simultaneous quantification of glucose uptake, mitochondrial membrane potential, and vascular parameters in murine flank tumors using quantitative diffuse reflectance and fluorescence spectroscopy

Biomed Opt Express. 2018 Jun 27;9(7):3399-3412. doi: 10.1364/BOE.9.003399. eCollection 2018 Jul 1.

Authors

Caigang Zhu¹, Hannah L Martin¹, Brian T Crouch¹, Amy F Martinez², Martin Li¹, Gregory M Palmer³, Mark W Dewhirst³, Nimmi Ramanujam¹

Affiliations

¹ Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
² Currently with Office of Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
³ Department of Radiation Oncology, Duke University, Durham, NC 27710, USA.

Abstract

The shifting metabolic landscape of aggressive tumors, with fluctuating oxygenation conditions and temporal changes in glycolysis and mitochondrial metabolism, is a critical phenomenon to study in order to understand negative treatment outcomes. Recently, we have demonstrated near-simultaneous optical imaging of mitochondrial membrane potential (MMP) and glucose uptake in non-tumor window chambers, using the fluorescent probes tetramethylrhodamine ethyl ester (TMRE) and 2-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG). Here, we demonstrate a complementary technique to perform near-simultaneous in vivo optical spectroscopy of tissue vascular parameters, glucose uptake, and MMP in a solid tumor model that is most often used for therapeutic studies. Our study demonstrates the potential of optical spectroscopy as an effective tool to quantify the vascular and metabolic characteristics of a tumor, which is an important step towards understanding the mechanisms underlying cancer progression, metastasis, and resistance to therapies.

Keywords: (170.4580) Optical diagnostics for medicine; (170.6280) Spectroscopy, fluorescence and luminescence; (170.6510) Spectroscopy, tissue diagnostics; (170.6935) Tissue characterization.