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Proceedings Paper

Optical monitoring of glucose demand and vascular delivery in a preclinical murine model
Author(s): Amy Frees; Narasimhan Rajaram; Sam McCachren; Alex Vaz; Mark Dewhirst; Nimmi Ramanujam
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Paper Abstract

Targeted therapies such as PI3K inhibition can affect tumor vasculature, and hence delivery of imaging agents like FDG, while independently modifying intrinsic glucose demand. Therefore, it is important to identify whether perceived changes in glucose uptake are caused by vascular or true metabolic changes. This study sought to develop an optical strategy for quantifying tissue glucose uptake free of cross-talk from tracer delivery effects. Glucose uptake kinetics were measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-Dglucose (2-NBDG), and 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-L-glucose (2-NBDLG) was used as a control to report on non-specific uptake. Vascular oxygenation (SO2) was calculated from wavelength-dependent hemoglobin absorption. We have previously shown that the rate of 2-NBDG delivery in vivo profoundly affects perceived demand. In this study, we investigated the potential of the ratio of 2-NBDG uptake to the rate of delivery (2-NBDG60/RD) to report on 2-NBDG demand in vivo free from confounding delivery effects. In normal murine tissue, we show that 2-NBDG60/RD can distinguish specific uptake from non-specific cell membrane binding, whereas fluorescence intensity alone cannot. The ratio 2-NBDG60/RD also correlates with blood glucose more strongly than 2-NBDG60 does in normal murine tissue. Additionally, 2-NBDG60/RD can distinguish normal murine tissue from a murine metastatic tumor across a range of SO2 values. The results presented here indicate that the ratio of 2-NBDG uptake to the rate of 2-NBDG delivery (2- NBDG60/RD) is superior to 2-NBDG intensity alone for quantifying changes in glucose demand.

Paper Details

Date Published: 4 March 2014
PDF: 8 pages
Proc. SPIE 8947, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XII, 894705 (4 March 2014); doi: 10.1117/12.2040950
Show Author Affiliations
Amy Frees, Duke Univ. (United States)
Narasimhan Rajaram, Duke Univ. (United States)
Sam McCachren, Duke Univ. (United States)
Alex Vaz, Duke Univ. (United States)
Mark Dewhirst, Duke Univ. (United States)
Nimmi Ramanujam, Duke Univ. (United States)

Published in SPIE Proceedings Vol. 8947:
Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XII
Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif, Editor(s)

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