Development and characterization of a novel, small animal external beam irradiator using a clinical high dose rate brachytherapy source

BACKGROUND: Pre-clinical in vivo characterization is a necessary step in the translation of novel radiotherapeutic interventions to clinical application. In vivo irradiations using a radioactive source like Ir-192 are challenging due to steep dose gradients and absence of universally available applicators that do not require physical contact or interstitial insertion. PURPOSE: To develop a novel external beam radiotherapy (EBRT) jig for accurate and reproducible radiotherapy treatments delivered using an Ir-192 source for in vivo studies. METHODS: An irradiation jig was constructed as a flat treatment bed and upright 6 cm diameter semi-circle with eight peripheral catheter positions encompassing the lateral side of a mouse. A CT scan was acquired of the jig along with a silicone phantom of a mouse with flank tumor. The scan was imported into Oncentra® for planning using 500 cGy prescribed to the tumor and calculated using TG43 and collapsed cone. EBT4 film and OSLD measurements verified dose distributions in the axial and coronal directions along with the entrance and exit dose to the tumor. Monte Carlo simulations using TOPAS™ were used to observe the 3D dose distribution within the tumor itself. Five female immunodeficient mice inoculated with HEC-1A cervical cancer tumors were irradiated and monitored for 3 weeks for tumor growth, body weight, and signs of toxicity. RESULTS: Dosimetry measurements agreed within 2%-15% of the tumor's entrance and exit dose as reported by Oncentra® using both computational formalisms. Monte Carlo simulations confirmed a uniform dose distribution within the tumor of ± 10%. Compared to unirradiated mice, a significant reduction in tumor growth post-irradiation was observed in all irradiated mice with no observable signs of toxicity. CONCLUSION: We have successfully developed an EBRT platform for in vivo irradiations with an Ir-192 source. The platform can be adapted for various tumor and sample sizes and other radioactive sources.