Application of 3D bioluminescent images to evaluate radiation treatment effect on mammary carcinoma cancer cells

Introduction: To monitor proliferation of metastatic breast cancer cells and to evaluate radiation treatment effect, metastasis of 4T1 cells and variation of quantitative photon radiance were evaluated using firefly luciferase-based 2D/3D bioluminescent images (BLIs). Detected deformed tumor volumes on 3D BLIs were registered with computed tomography (CT) images to explore the possibilities for adaptive radiotherapy plans. Materials and Methods: Metastatic 4T1 cells were injected into mammary glands of 8 BALB/c mice. The 2D and 3D BLIs were acquired every 2-3 days for a month and radiance (the number of photons/area/time/solid angle) variation of emitted bioluminescent light was analyzed by injecting luciferine. After 1 week, radiation dose of 20 Gy in a single fraction was delivered in an orthovoltage treatment unit. Detected cancer cells were overlaid on morphologic photographs of mice to overall figure out position and growing volumes in 2D BLIs. Specific coordinates of primary and metastasized cancer cells were slice-by-slice verified in 3D BLI. To define molecular cancer cells on CT images, 3D BLI were registered with the anatomical images using a surface matching algorithm. Results and Discussion: The 3D BLI facilitated early detection of cancer cells and evaluation of tumor progression, metastasis, and necrosis. Treated mice with only primary tumor volumes showed 67% reduction of bioluminescent signals, while mice with metastatic tumor volumes 88% reduction as compared to the control group. Registration of 3D BLIs with CT images guided molecular cancer cells on anatomical coordinates. In conclusion, 3D BLIs were useful to detect pathoformic metastasis and to define molecular cancer cells. BLIs contributed to quantify radiation response to differentiate molecular tumor volumes on CT images. Tracking of cancer cells on BLIs would be employed to reflect characteristics of cancer cells for adaptive radiation treatment.