Dynamic contrast-enhanced MRI evaluates the early response of human head and neck tumor xenografts following anti-EMMPRIN therapy with cisplatin or irradiation

J Magn Reson Imaging. 2015 Oct;42(4):936-45. doi: 10.1002/jmri.24871. Epub 2015 Feb 20.

Abstract

Purpose: To assess the early therapeutic effects of anti-EMMPRIN (extracellular matrix metalloprotease inducer) antibody with/without cisplatin or X-ray radiation in head and neck cancer mouse models using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Materials and methods: Mice bearing SCC1 (or OSC19) tumor xenografts were treated with anti-EMMPRIN antibody, radiation, cisplatin, or anti-EMMPRIN antibody plus cisplatin (or radiation) for a week (n = 4-5 per group). DCE-MRI was carried out on a 9.4T small animal MR scanner on days 0, 3, and 7, and K(trans) values were averaged in a 0.5-mm-thick peripheral tumor region. Ki67 and CD31 staining were implemented for all tumors after imaging.

Results: The K(trans) changes of SCC1 and OSC19 tumors treated with anti-EMMPRIN antibody for 3 days were -18 ± 8% and 4 ± 7%, respectively, which were significantly lower than those of control groups (39 ± 5% and 45 ± 7%; P = 0.0025 and 0.0220, respectively). When cisplatin was added, those were -42 ± 9% and -44 ± 9%, respectively, and with radiation, -45 ± 9% and -27 ± 10%, respectively, which were also significantly lower than those of control groups (P < 0.0001 for all four comparisons). In the eight groups untreated (served as control) or treated with anti-EMMPRIN antibody with/without cisplatin or radiation, the mean K(trans) change for 3 days was significantly correlated with the mean tumor volume change for 7 days (r = 0.74, P = 0.0346), Ki67-expressing cell density (r = 0.96, P = 0.0001), and CD31 density (r = 0.84, P = 0.0084).

Conclusion: DCE-MRI might be utilized to assess the early therapeutic effects of anti-EMMPRIN antibody with/without chemotherapy or radiotherapy in head and neck cancer.

Keywords: DCE-MRI; anti-EMMPRIN antibody; cisplatin; head and neck cancer; radiotherapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Basigin / immunology
  • Cell Line, Tumor
  • Chemoradiotherapy / methods*
  • Cisplatin / therapeutic use
  • Contrast Media
  • Drug Monitoring / methods
  • Early Detection of Cancer
  • Female
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Nude
  • Prognosis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Contrast Media
  • Basigin
  • Cisplatin