Bioluminescence Tomography Guided Small-Animal Radiation Therapy and Tumor Response Assessment

Abstract

Purpose: The image guided small animal arc radiation treatment platform has adopted onboard cone beam computed tomography and bioluminescence tomography (BLT). We used BLT to guide irradiation delivery and quantitatively assess irradiation-induced tumor response.

Methods and materials: BLT 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 either received radiation treatment (radiation therapy [RT] group, n = 9) or did not (control group, n = 9). BLT was used to guide delivery of a single-fraction 5-Gy radiation dose to the tumor and to evaluate the treatment response. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining was used to evaluate irradiation-induced DNA damage and cell apoptosis.

Results: Phantom 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 group of animals, there was significant reduction in both the BLT-based tumor volume (21% ± 10%, P = .001) and bioluminescence intensity (48% ± 17%, P = .0008). For the control group, a significant increase was detected in the BLT tumor volume (35% ± 12%, P < .0001) but not the BLT bioluminescence intensity (P = .4). There was a significant difference in the BLT tumor volume between the RT and control groups 7 days after irradiation (P = .03). Regression analysis suggests a strong correlation between the BLT and cone beam computed tomography tumor volume (R² = 0.93). Analysis using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining showed a significant difference in tumor cell apoptosis between the RT and control groups (20.6% ± 2.9% and 3.2% ± 1.7%, respectively; P < .05).

Conclusions: BLT onboard the image guided small animal arc radiation treatment platform can be used to accurately guide irradiation delivery and to quantitatively assess treatment response by simultaneously monitoring tumor volume and cancer cell population.