Comparison of Bioluminescence and Fluorescence Imaging as Tools for Evaluating Growth of MCF7 and 4T1 Mammary Tumors
Lin, Elisa B.
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INTRODUCTION: Tumor growth can be assessed by a variety of small animal imaging modalities which are cheap, easy, and efficient. In particular, bioluminescence imaging (BLI) and fluorescence imaging (FLI) have received attention for their ability to measure tumor growth and response to treatment. Both imaging modalities are accurate and well established, however, each method has its own unique advantages and limitations. This study compared the use of BLI and FLI to characterize and monitor growth of mammary 4T1-luc and MCF7-luc-GFP-mCherry tumors in nude mice. Strong correlations were established between BLI, FLI, and tumor volume, providing evidence that each method could be used to validate the other and reduce overall error. METHODS: BLI and FLI image sequences were performed with the IVIS(r) Spectrum. BLI was used for 4T1 (n = 8) and MCF7 (n = 6) tumors. FLI was only used for MCF7 tumors. Tumor volume was measured with calipers. RESULTS: Evaluating the area under each BLI and FLI curve (the AUC method) proved to be more accurate than only evaluating at one time point or wavelength. For both BLI and FLI, the AUC method greatly simplified the imaging workflow and removed the need for perfect temporal accuracy, since all times and wavelengths were considered. BLI and FLI both showed strong correlation with tumor volume (R2 = 0.91 and 0.87, respectively). The BLI and FLI signals were also correlated (R2 = 0.79). Experimental difficulties like tumor scarring and a mid-experiment C. bovis infection compromised data quality. DISCUSSION: The strong correlations between each measurement are very reassuring. Each offers specific benefits, e.g., BLI and FLI allow detection of sub-palpable volumes and additional metastases in some cases. BLI offers particularly strong contrast to noise, but requires the administration of luciferin substrate. FLI signal is subject to background auto fluorescence; this became a particular problem when the C. bovis infection occurred. Caliper measurements are simple for subcutaneous tumors, but the optical imaging can also reveal deeper tumors. The investigations to date largely confirm growth characteristics and the utility of available imaging methods matching the extant literature. The correlations had not been examined for 4T1-luc at UTSW previously. Furthermore, these methods provide a foundation for my forthcoming medical school research activity. Notably, future plans include continued investigation of metastases and utilizing Multispectral Optoacoustic Tomography (MSOT) for integrated hypoxia studies.