Conventional in vivo irradiation procedures are insufficient to accurately determine tumor responses to non-uniform radiation fields

Abstract

Purpose: To determine differences in overall tumor responses measured by volumetric assessment and bioluminescence imaging (BLI) following exposure to uniform and non-uniform radiation fields in an ectopic prostate tumor model.

Materials and methods: Bioluminescent human prostate tumor xenografts were established by subcutaneous implantation into male mice. Tumors were irradiated with uniform or non-uniform field configurations using conventional in vivo irradiation procedures performed using a 225 kVp generator with custom lead shielding. Tumor responses were measured using Vernier calipers and by BLI using an in vivo imaging system. Survival was defined as the time to quadroupling of pre-treatment tumor volume.

Results: The correlation between BLI and tumor volume measurements was found to be different for un-irradiated (R = 0.61), uniformly irradiated (R = 0.34) and partially irradiated (R = 0.30) tumors. Uniformly irradiated tumors resulted in an average tumor growth delay of 60 days with median survival of 75 days, compared to partially irradiated tumors which showed an average growth delay of 24 days and median survival of 38 days.

Conclusions: Correlation between BLI and tumor volume measurements is lower for partially irradiated tumors than those exposed to uniform dose distributions. The response of partially irradiated tumors suggests non-uniformity in response beyond physical dose distribution within the target volume. Dosimetric uncertainty associated with conventional in vivo irradiation procedures prohibits their ability to accurately determine tumor response to non-uniform radiation fields and stresses the need for image guided small animal radiation research platforms.

Keywords::

• Bystander
• bioluminescent imaging
• non-uniform
• in vivo
• tumor burden

Acknowledgements

We would like to acknowledge Dr Conor McGarry at the Northern Ireland Cancer Centre for his useful insight concerning this project. This work is supported by Cancer Research UK (C1513/A7047 to KMP and C212/A11342 for ARH) and Friends of The Cancer Centre (Registered Charity NI00080).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.