Abstract 102: A longitudinal, orthotopic mouse imaging model using modified hNIS-A549 human lung adenocarcinoma cells and SPECT/CT imaging

Abstract

Abstract The human sodium iodide symporter (hNIS; SLC5A5) is a membrane glycoprotein that is a transporter for iodide uptake and also concentrates the radiotracer technetium 99mTc-pertechnetate (99mTc). In this study, we investigated the use of hNIS as an imaging reporter gene expressed in lung cancer cells in nude mice that can be quantified using single-photon emission computed tomography (SPECT) imaging. The radionuclide 99mTc was selected for its rapid clearance from the body and its short physical half-life (i.e., 6 hours). These characteristics allowed for the development a highly sensitive spatial and temporal tumor-imaging model. Human lung adenocarcinoma A549 cells were genetically modified using plasmid and lentiviral vectors to stably express hNIS. Using these modified cells, we monitored xenograft and orthotopic tumor growth using SPECT/CT for a total of 47 days. hNIS expression was quantified using qPCR and tumor progression was monitored by SPECT voxel analysis and validated using H&E staining of pulmonary tumors. hNIS-lentiviral vector tumors exhibited significant 99mTc uptake over hNIS-plasmid vector cells and A549 unmodified control cells in vitro and in vivo. Furthermore, this mouse study achieved a 100% orthotopic tumor take rate. Thus, a highly sensitive preclinical imaging mouse lung cancer model was developed. This model can be imaged longitudinally, which is made possible through the stable incorporation of hNIS into the tumor cell, allowing for 99mTc uptake and SPECT/CT analysis of tumor burden. In future studies, we will investigate whether chemotherapeutic regimens can effectively reduce the growth of hNIS-expressing A549 tumors over time using this preclinical in vivo model. This novel lung cancer animal model could significantly reduce animal numbers, improve the quality of data by avoiding inter-animal variation, and allow for longitudinal analysis and efficacy of experimental chemotherapeutics. Citation Format: Amber Alane McBride, Dominique Nicole Price, Jeffrey P. Norenberg, Debra A. MacKenzie, Todd Anthony Thompson, Pavan Muttil. A longitudinal, orthotopic mouse imaging model using modified hNIS-A549 human lung adenocarcinoma cells and SPECT/CT imaging. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 102. doi:10.1158/1538-7445.AM2014-102