Rationale and objectives: The purpose of this study was to evaluate whether "steady state" magnetic resonance imaging (MRI) using a robust multiecho ΔR2* MR relaxometry technique is suitable for the early assessment of a clinically approved antiangiogenic treatment regimen using bevacizumab (Avastin).
Methods: A673 rhabdomyosarcoma-bearing mice were treated with bevacizumab (n = 6) or saline as control, respectively (n = 6). MRI using a multigradient echo sequence was performed before and after 2 doses of 100 μg bevacizumab at baseline and day 7. Ultrasmall superparamagnetic iron oxide particles (SH U 555 C) induced changes of the transverse relaxation rate R2* (ΔR2*) were measured in regions of interest. From these results, the vascular volume fraction was estimated, providing a surrogate marker for the microvessel density (MVD). The actual MVD was determined by immunohistochemistry and correlated with the MRI results.
Results: Bevacizumab treatment resulted in a significant reduction of the ΔR2* values compared with the control group (bevacizumab: 10.47 ± 0.78 seconds(-1) vs. control: 17.91 ± 2.63 seconds(-1); P = 0.01), reflecting the significant decrease of the vascular volume fraction by 33% (bevacizumab: 2.21% ± 0.15% vs. control: 3.31% ± 0.22%; P = 0.001). Immunohistochemistry confirmed the MR results showing an approximately 25% reduction of the MVD after treatment (bevacizumab: 7.11 ± 0.3 vs. control: 9.45 ± 0.38; P = 0.001).
Conclusion: Multiecho ΔR2* MR relaxometry allows an early and quantitative assessment of tumor vascularization changes in response to an antiangiogenic treatment with a clinically approved vascular endothelial growth factor inhibitor. With the availability of long circulating ultrasmall superparamagnetic iron oxide particles s for clinical use, this imaging technique could be instantly translated to antiangiogenic treatment monitoring in clinical studies.