Characterization and performance of a near-infrared 2-deoxyglucose optical imaging agent for mouse cancer models

Authors

Joy L. Kovar, LI-COR Biosciences, Lincoln, NEFollow
William Volcheck, LI-COR Biosciences, Lincoln, NE
Eva Sevick-Muraca, Baylor College of Medicine
Melanie A. Simpson, University of Nebraska at LincolnFollow
D. Michael Olive, LI-COR Biosciences, Lincoln, NE

Document Type

Article

Date of this Version

1-2009

Comments

Published in Analytical Biochemistry 384:2 (January 15, 2009), pp. 254–262; doi: 10.1016/j.ab.2008.09.050 Copyright © 2008 Elsevier Inc. Used by permission. http://www.elsevier.com/locate/yabio

Abstract

Malignant neoplasms exhibit an elevated rate of glycolysis over normal cells. This characteristic can be exploited for optical imaging of tumors in mice. A near-infrared fluorophore, IRDye 800CW, emission maximum 794 nm, was conjugated to 2-deoxyglucose (2-DG). An immunofluorescent cell-based assay was used to evaluate specificity and sensitivity of the conjugate in cultured cell monolayers. Dose-dependent uptake was established with increasing concentrations of IRDye 800CW 2-DG for epithelial and prostate carcinomas. IRDye 800CW 2-DG was specifically blocked by an antibody against GLUT1 glucose transporter, and by excess unlabeled 2-DG or d-glucose. Signal was increased by a phorbol ester activator of glucose transport. Fluorescence microscopy data confirmed localization of the conjugate in the cytoplasm. Subsequent in vivo studies optimized dose, clearance, and timing for signal capture in nude mouse xenografts. In all cases, tumors were clearly imaged with good signal-to-noise characteristics. These data indicate that IRDye 800CW 2-DG is a broadly applicable optical imaging agent for in vivo imaging of neoplasms in mice.