Evaluation of chemotherapeutic response of temozolomide in orthotopic glioma using bioluminescence tomography

摘要

Glioma is one of the most important leading causes of cancer-related deaths worldwide. Temozolomide (TMZ) is a DNA methylating agent that presents promising antitumor activity against high grade glioma. However, there is no effective way to assess the therapeutic response to TMZ at early stage. In this study, we evaluated the efficacy of TMZ on brain tumor through bioluminescence tomography (BLT) based on multi-modality imaging system. Initially, the human glioma cell line U87MG-fLuc cells were cultured, and the orthotopic mouse brain tumor model was established. 10 days after the tumor cell implantation, the mice were divided into two groups including the TMZ group and the control group. The mice in the TMZ group were treated with Temozolomide with dosage of 50 mg/kg/day intraperitoneally for continuous 6 days, and the mice in the control group were treated with sterile saline at equal volume. The bioluminescence imaging (BLI) was acquired every 5 days for monitoring the therapeutic responses. A randomly enhanced adaptive subspace pursuit (REASP) algorithm is presented for bioluminescence tomography reconstruction. Basically, numerical experiments were used to validate the efficiency of the proposed method, and then the mice's CT and BLI data were acquired to reconstruct BLT using the REASP algorithm. The results in this study showed that the growth of glioma can be monitored from very early stage, and the TMZ treatment efficacy can be reliably and objectively assessed using BLT method. Our data demonstrated TMZ can effectively inhibit the tumor growth.