Dynamic Contrast-Enhanced MRI Evaluates the Early Response of Human Head and Neck Tumor Xenografts Following Anti-EMMPRIN Therapy With Cisplatin or Irradiation

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.