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

Radiother Oncol. 2014 Feb;110(2):335-41. doi: 10.1016/j.radonc.2013.10.018. Epub 2013 Nov 11.

Abstract

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 ve 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.

Keywords: Cervical carcinoma xenografts; DCE-MRI; Hypoxia; Metastasis; Radioresponsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / physiology
  • Cell Survival / physiology
  • Contrast Media
  • Female
  • Gadolinium DTPA*
  • Humans
  • Lymphatic Metastasis
  • Magnetic Resonance Imaging / methods
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nitroimidazoles / pharmacology
  • Radiation-Sensitizing Agents / pharmacology
  • Radionuclide Imaging
  • Uterine Cervical Neoplasms / diagnostic imaging
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*
  • Xenograft Model Antitumor Assays

Substances

  • Contrast Media
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • pimonidazole
  • Gadolinium DTPA