Detection of metastatic tumors after gamma-irradiation using longitudinal molecular imaging and gene expression profiling of metastatic tumor nodules

Abstract

A few recent reports have indicated that metastatic growth of several human cancer cells could be promoted by radiotherapy. C6-L cells expressing the firefly luciferase (fLuc) gene were implanted subcutaneously into the right thigh of BALB/cnu/nu mice. C6-L xenograft mice were treated locally with 50-Gy gamma-irradiation (gamma-IR) in five 10-Gy fractions. Metastatic tumors were evaluated after gamma-IR by imaging techniques. Total RNA from non-irradiated primary tumor (NRPT), gamma-irradiated primary tumor (RPT), and three metastatic lung nodule was isolated and analyzed by microarray. Metastatic lung nodules were detected by BLI and PET/CT after 6-9 weeks of gamma-IR in 6 (17.1%) of the 35 mice. The images clearly demonstrated high [F-18]FLT and [18F]FDG uptake into metastatic lung nodules. Whole mRNA expression patterns were analyzed by microarray to elucidate the changes among NRPT, RPT and metastatic lung nodules after gamma-IR. In particular, expression changes in the cancer stem cell markers were highly significant in RPT. We observed the metastatic tumors after gamma-IR in a tumor-bearing animal model using molecular imaging methods and analyzed the gene expression profile to elucidate genetic changes after gamma-IR.