Validating Bioluminescence Imaging as a High-Throughput, Quantitative Modality for Assessing Tumor Burden

Abstract

Bioluminescence imaging (BLI) is a highly sensitive tool for visualizing tumors, neoplastic development, metastatic spread, and response to therapy. Although BLI has engendered much excitement due to its apparent simplicity and ease of implementation, few rigorous studies have been presented to validate the measurements. Here, we characterize the nature of bioluminescence output from mice bearing subcutaneous luciferase-expressing tumors over a 4-week period. Following intraperitoneal or direct intratumoral administration of luciferin substrate, there was a highly dynamic kinetic profile of light emission. Although bioluminescence was subject to variability, strong correlations (r > .8, p < .001) between caliper measured tumor volumes and peak light signal, area under light signal curve and light emission at specific time points were determined. Moreover, the profile of tumor growth, as monitored with bioluminescence, closely resembled that for caliper measurements. The study shows that despite the dynamic and variable nature of bioluminescence, where appropriate experimental precautions are taken, single time point BLI may be useful for noninvasive, high-throughput, quantitative assessment of tumor burden. Mol Imaging (2004) 3, 117 -124.

Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI

“…Signal is attenuated at depth, but the technique can be applied routinely in both SC models and for monitoring orthotopic tumor development (3)(4)(5)(6)(7)(8)12 Author Manuscript calipers or MRI (5,12,38,39). In our early work we found strong correlations (r>0.8) between peak light signal, initial area under the curve, or signal intensity at 10 minutes post luciferin infusion and tumor volume following IP administration of 150 mg/kg D-luciferin (12). However individual measurements showed discrepancies and consecutive observations could vary by as much as 60%.…”

“…Bioluminescence imaging has also found widespread use in examining changes in tumor growth over a period of many weeks with diverse therapies (6)(7)(8)(9)(10). Bioluminescent imaging requires administration of luciferin substrate, which may be achieved by multiple routes including intravenous (IV), intra peritoneal (IP) or subcutaneous (SC) (11,12). Luciferin is then carried throughout the vasculature and has been shown to readily permeate every region of the body (9,13,14).…”

Real-time bioluminescence and tomographic imaging of gastric cancer in a novel orthotopic mouse model

“…Bioluminescence imaging (BLI), especially, demonstrates the most desirable combination of high sensitivity and easy handling (5) and is suitable for acquire signal deep in tissue (6). It has been widely used for monitoring different cancer biological processes [angiogenesis (7,8), infinite proliferation and meta stasis (9,10), multidrug resistance (11,12)] and assessing the efficacy of different therapeutic modalities (13)(14)(15).…”

Bioluminescence imaging in bone tissue engineering

“…Tissue particularly attenuates light with a wavelength in the range of 400 to 600nm, but less between 600 to 950nm [192]. Indeed, we observed that (pigmented) hair and skin absorbed much light, as reported [193]. In principle, the light intensity is attenuated approximately 10-fold for every centimetre of tissue depth [194].…”