Improved Pre-clinical Radiation Treatment Techniques for a Novel Mouse Model of Head-and-neck Cancer

Abstract

Mice are the predominant animal model used in radiation therapy research for investigating radiobiological kinetics and evaluating new therapeutics to achieve a higher therapeutic ratio in the clinic. A novel carcinogen-induced and genetically engineered head and neck squamous cell carcinoma mouse model was developed at Duke to study head and neck cancer, one of the most widely spread cancers in the world. However, platforms that are able to perform precise and reproducible radiation therapy on these mice to mimic human radiation therapy are lacking. To address this issue, a platform based on the X-RAD 225Cx orthovoltage irradiator was developed. 3D printing technique was used to generate imaging phantoms, immobilization devices, and blocks. A simulation was conducted to optimize imaging protocol. Results were verified on the measurement on both the 3D-printed phantom and the actual mouse. Prior to irradiation, mice were placed on the immobilization device in a supine position, and the isocenter was determined by the position of the device since the irradiator does not have a laser localizer system. The performance of the immobilization was obtained by scanning several mice separately at various time points, ranging from several hours post-imaging to two months post-imaging. In order to make up the deficiency that irradiator only have rectangular and circular collimators which cannot provide moderate protection for organs at risk. Blocks with 3% transmission were designed based on the contours of central nervous system by a state-of-art program, BlockGen.A protocol was developed for immobilization and image acquisition. 60 kVp was found to give the highest contrast of iodine, so it was set as the tube voltage for image acquisition. The deviations of positioning, i.e. the same mouse in separate scanning, are measured as 0.22±0.44 mm in LR axis, 0.15±0.30 mm in PA axis, and -0.24±0.25 mm in IS axis. Blocks with a 1.5 mm margin which can shield brain and spinal cord even in the worst case, were printed for opposed lateral beams; they were verified on fluoroscopy. The block system was modified to eliminate potential human errors. Comparison on brain and spinal cord among different mice showed the largest deviation in 2.6 mm, however, with manually selection of the middle one, 1.5 mm margin is enough to shield central nervous system. Indicating that a generic block could be used in the experiment that does not require a very accurate treatment. The generic block can significant save time and effort for preclinical radiation treatment experiment. In this study, a platform that is capable of enhancing contrast imaging and allowing precise radiation therapy to be performed on genetically-engineered mice with head and neck cancer has been developed. This paves the way for more accurate head and neck mice model radiation therapy studies. In addition, the platform could be used in other types of preclinical studies.