DCE-MRI of the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinoma xenografts

Background and purpose: Locoregional treatment failure and poor survival rates are associated with extensive hypoxia in the primary tumor in advanced cervical carcinoma. The potential of gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the hypoxic fraction, radioresponsiveness, and metastatic propensity of cervical carcinomas was investigated in this preclinical study. Materials and methods: CK-160 and TS-415 cervical carcinoma xenografts were used as tumor models. DCE-MRI was carried out at 1.5 T, and parametric images of K-trans and v(e) were produced by pharmacokinetic analysis of the DCE-MRI series. Pimonidazole was used as a hypoxia marker. Tumor radioresponsiveness was determined by irradiating tumors with five fractions of 4 Gy in 48 h and measuring cell survival in vitro. Metastatic propensity was determined by examining host mice for tumor growth in lymph nodes. Results: Low values of K-trans were associated with extensive hypoxia and radiation resistance in tumors of both lines and with high incidence of metastases in CK-160 tumors. Associations between v(e) and hypoxia, radioresponsiveness, or metastatic propensity were not found in any of the tumor lines. Conclusion: K-trans is a potentially useful biomarker of tumor hypoxia, radiation resistance, and metastatic growth in advanced cervical carcinoma. (C) 2013 Elsevier Ireland Ltd. All rights reserved.