Abstract 5242: Bioluminescence imaging of radiation induced tumor growth inhibition in orthotopic mouse models
Authors: Baugher Meridith , Ziemke Matt , Trachet Erin , Elliott William , Leopold Wilbur R. , McConville Patrick 
Published: February 2011

Introduction: Radiation therapy continues to be a standard of care for many cancer indications including brain and prostate. Commonly, strategies for development of new chemotherapies encompass intended combination therapy with radiation. Preclinical methods for using localized radiation therapy against tumors in specific tissues may increase clinical relevance and predictive power of the models. The ability to non-invasively detect tumor burden and radiation response in deep tissue tumors would be an additional advantage. We describe application of localized radiation therapy in two orthotopic tumor models with parallel luciferase driven imaging of tumor burden and response.

Methods: Human prostate and brain tumor cell lines transfected to constitutively express luciferase were used in these studies. For the prostate orthotopic, PC-3M-luc-C6 prostate carcinoma cells (5 × 105 cells in 20µl) were injected into the dorsal prostatic lobe of male nu/nu mice on Day 0. For the brain orthotopic, U87MG-luc glioma cells (106 cells in 10µl) were injected by stereotax 2mm right lateral and 1mm anterior to the coronal suture at a depth of 2mm. At staging (prostate: Day 7; brain: Day 27) animals were injected with 150mg/kg luciferin and imaged using bioluminescence. The tumors were segmented and total light output in photons/sec used to quantify tumor burden and select mice to go into two groups (prostate: n=10; brain: n=8) matched for mean tumor burden. In each case, Group 1 was untreated and Group 2 was treated using 2.5 Gy radiation (QDx5; 2 off) x2wk, with a lead shielded holder used to localize the dose to the prostate or brain regions. Bioluminescence imaging was used to assess tumor burden and treatment response over time in each model.

Results and Discussion: Radiation therapy at 15 Gy on a (QDx5;2off)x2wk schedule was tolerated, producing 3% and 13% mean body weight loss in the prostate and brain tumored mice respectively. Bioluminescence imaging enabled a highly sensitive and quantitative end point for tumor burden in both cases, and highlighted localization of the tumor growth to the tissues in question. The treatments resulted in significant tumor growth inhibition compared with controls. Radiation resulted in approximate tumor stasis in both cases, with T/C values of 6% (4 weeks post-Rx) and 43% (1 week post-Rx) in the prostate and brain tumor models, respectively. The luciferase based imaging approach coupled with localized radiation treatment enables a quantitative model for deep tissue tumor targeted combination chemotherapy/radiation treatment strategies in preclinical models. This approach may facilitate development of new molecules for future use with radiation, including optimization of schedule and timing.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5242.