Dynamic contrast-enhanced magnetic resonance imaging for monitoring the anti-angiogenesis efficacy in a C6 glioma rat model

Acta Radiol. 2020 Jul;61(7):973-982. doi: 10.1177/0284185119887598. Epub 2019 Nov 18.

Abstract

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful in predicting responses to angiogenic therapy of malignant tumors.

Purpose: To observe the dynamics of DCE-MRI parameters in evaluating early effects of antiangiogenic therapy in a C6 glioma rat model.

Material and methods: The Bevacizumab or vehicle treatment was started from the 14th day after glioma model was established. The treated and control groups (n = 13 per group) underwent DCE-MRI scans on days 0, 1, 3, 5, and 7 after treatment. Tumor volume was calculated according to T2-weighted images. Hematoxylin and eosin, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) examination were performed on day 7. The MRI parameters between the two groups were compared and correlations with immunohistochemical scores were analyzed.

Results: The average tumor volume of treated group was significantly lower than that of control group on day 7 (81.764 ± 1.043 vs. 103.634 ± 3.868 mm3, P = 0.002). Ktrans and Kep decreased in the treated group while they increased in the control group. The differences were observed on day 5 (Ktrans: 0.045 ± 0.018 vs. 0.093 ± 0.014 min-1, P < 0.001; Kep: 0.062 ± 0.018 vs. 0.134 ± 0.047 min-1, P = 0.005) and day 7 (Ktrans: 0.032 ± 0.010 vs. 0.115 ± 0.025 min-1, P < 0.001; Kep: 0.045 ± 0.016 vs. 0.144 ± 0.042 min-1, P < 0.001). The difference of Ve was observed on day 5 (0.847 ± 0.248 vs. 0.397 ± 0.151, P = 0.009) and 7 (0.920 ± 0.154 vs. 0.364 ± 0.105, P = 0.006). Ktrans and Kep showed positive correlations with MVD and Ve showed negative correlation with PCNA.

Conclusion: DCE-MRI can assess the changes of early effects of anti-angiogenic therapy in preclinical practice.

Keywords: Dynamic contrast-enhanced magnetic resonance imaging; angiogenesis; glioma; therapy.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Bevacizumab / pharmacology*
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / drug therapy*
  • Contrast Media
  • Disease Models, Animal
  • Gadolinium DTPA
  • Glioma / diagnostic imaging*
  • Glioma / drug therapy*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Microvessels
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Burden

Substances

  • Angiogenesis Inhibitors
  • Contrast Media
  • Bevacizumab
  • gadodiamide
  • Gadolinium DTPA