Bioluminescence Tomography Guided Small Animal Radiotherapy and Tumor Response Assessment

Publication date: Available online 2 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Junwei Shi, Thirupandiyur S. Udayakumar, Keying Xu, Nesrin Dogan, Alan Pollack, Yidong Yang
Purposes: The image-guided SMall Animal Arc Radiation Treatment platform (iSMAART) has adopted onboard cone beam computed tomography (CBCT) and bioluminescence tomography (BLT). In this study, we used BLT to guide radiation delivery and quantitatively assess radiation-induced tumor response.Methods and MaterialsBLT was first validated on a tissue-simulating phantom, where the internal chemiluminescent liquid had a constant volume while its luminescence intensity gradually decayed. Then, in vivo experiments were performed on BALB/c mice orthotopically inoculated with 4T1 breast carcinoma cells expressing luciferase. Animals received either radiation treatment (RT group, n=9) or not (Control group, n=9). BLT was used to guide delivery of a single fraction of 5 Gy radiation dose to the tumor, and to evaluate the treatment response. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to evaluate the radiation-induced DNA damage and cell apoptosis.ResultsPhantom results showed that BLT not only recovered the constant target volume with <2% deviation, but also accurately monitored the decay of the chemiluminescent molecules. For the RT animal group, there was significant reduction in both BLT-based tumor volume (21±10%, P=0.001) and bioluminescence intensity (48±17%, P=0.0008). For the control group, the significant increase was detected in the BLT tumor volume (35±12%, P<0.0001), but not in the BLT bioluminescence intensity (P=0.4). There was a significant difference in the BLT tumor volume between the RT and control group 7 days after radiation (P=0.03). Regression analysis suggests a strong correlation between the BLT and CBCT tumor volume (R²=0.93). The TUNEL staining analysis showed a significant difference in tumor cell apoptosis between the RT and control group (20.6±2.9% vs 3.2±1.7%, P<0.05).ConclusionBLT onboard the iSMAART can be used to accurately guide radiation delivery, and to quantitatively assess treatment response by simultaneously monitoring tumor volume and cancer cell population.



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