Abstract 2871: Non-invasive monitoring of the efficacy of anticancer therapeutic agent in lung orthotopic xenograft models of NSCLC using Bio-Luminescence Imaging (BLI)

Abstract

Abstract Non-Small Cell Lung Cancer (NSCLC) patients have a poor rate of survival owing to diagnosis at a later stage. This necessitates development of novel therapeutic strategies that limit rapid progression of NSCLC and imaging techniques that monitor such changes in vivo. There has been a significant growth of bioluminescence imaging applications in small laboratory animal models in recent years, owing to its high sensitivity, efficiency, and non-invasive nature. Our lab has previously demonstrated that a therapeutic agent that disrupts mitochondrial respiration effectively hampers proliferation of NSCLC cell lines in vitro. With an effort to investigate the potential of this therapeutic agent in clinical settings, we used a lung orthotopic xenograft mouse model along with bioluminescence imaging (BLI) to continuously monitor the efficacy of the drug in vivo. Briefly, we implanted NSCLC cell line transduced with lentiviral particles carrying luciferase sequence, in the left lung of 6-8 weeks old female NOD/SCID mice to generate lung orthotopic xenografts. The therapeutic agent was administered intravenously over several weeks. Tumor growth was then compared between the untreated versus the treated mice, non-invasively through bioluminescence imaging (Perkin Elmer’s IVIS Lumina III Imager). On sacrificing the mice, the lungs were harvested, formalin fixed and paraffin embedded for Immunohistochemistry. Our BLI data show that in the mice treated with the therapeutic agent, tumors are localized to the left lung (site of implantation) as opposed to the control mice where the tumors metastasized to the right lung. The BLI data indicates significant decrease in radiance (total flux in photons per second) in mice subjected to treatment when compared to control mice. We show that the therapeutic agent significantly inhibits progression and metastasis of human NSCLC cell line orthotopically injected in the lungs of NOD/SCID mice. The results suggest that it might be potent anti-cancer drug as it is effective in a model that recapitulates the natural environment of lung tumorigenesis. Immunohistochemical studies are underway to discern the mechanistic details. Citation Format: Sanchareeka Dey, Sarada Preeta Kalainayakan, Poorva Ghosh, Li Zhang. Non-invasive monitoring of the efficacy of anticancer therapeutic agent in lung orthotopic xenograft models of NSCLC using Bio-Luminescence Imaging (BLI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2871. doi:10.1158/1538-7445.AM2017-2871