The Influence of Hypoxia and pH on Bioluminescence Imaging of Luciferase-Transfected Tumor Cells and Xenografts.

Ashraf A Khalil,Elizabeth Rosenberg,Kristoffer Valerie,Mark J Jameson,Sarah E Golding,Peck Sun Lin,Seth M Dever,Theodore D Chung,William C Broaddus

doi:10.1155/2013/287697

Abstract

Bioluminescence imaging (BLI) is a relatively new noninvasive technology used for quantitative assessment of tumor growth and therapeutic effect in living animal models. BLI involves the generation of light by luciferase-expressing cells following administration of the substrate luciferin in the presence of oxygen and ATP. In the present study, the effects of hypoxia, hypoperfusion, and pH on BLI signal (BLS) intensity were evaluated in vitro using cultured cells and in vivo using a xenograft model in nude mice. The intensity of the BLS was significantly reduced in the presence of acute and chronic hypoxia. Changes in cell density, viability, and pH also affected BLS. Although BLI is a convenient non-invasive tool for tumor assessment, these factors should be considered when interpreting BLS intensity, especially in solid tumors that could be hypoxic due to rapid growth, inadequate blood supply, and/or treatment.

Highlights

In vivo bioluminescence imaging (BLI) is a technology that is frequently used in the study of animal tumor models [1]
Oxygen available for the BLI reaction could be reduced to limiting levels, which would result in a reduced BLI signal (BLS) and underestimation of the actual tumor size [14]
In the process of developing an in vivo BLI-based mouse model of U87 glioma cells for evaluation of radiotherapy, we noted that these solid tumors frequently become transiently or chronically hypoxic and that, in this situation, tumor growth determined by BLI may be an underestimate

Summary

Introduction

In vivo bioluminescence imaging (BLI) is a technology that is frequently used in the study of animal tumor models [1]. Tumor hypoxia can develop as a result of treatment [13] In these settings, oxygen available for the BLI reaction could be reduced to limiting levels, which would result in a reduced BLI signal (BLS) and underestimation of the actual tumor size [14]. In the process of developing an in vivo BLI-based mouse model of U87 glioma cells for evaluation of radiotherapy, we noted that these solid tumors frequently become transiently or chronically hypoxic and that, in this situation, tumor growth determined by BLI may be an underestimate. The in vitro and in vivo results indicate that the development of hypoxia or pH changes could impact the use of BLI in quantitative studies of tumor growth and treatment response

Materials and Methods

Results and Discussion

Conclusions