Multiparametric MR imaging of tumor response to intraarterial chemotherapy in orthotopic xenograft models of human metastatic brain tumor.

Abstract

The purpose of our study was to investigate the therapeutic efficacy of intraarterial (IA) chemotherapy via multiparametric magnetic resonance imaging (MRI) analysis in orthotopic mouse brain tumor models. Stereotactic-guided intracranial inoculation of MDA-MB-231 cells was performed in nude mice. Thirty tumor bearing mice were randomized into three groups, and each group received either IA docetaxel administration (n = 10), intravenous (IV) docetaxel administration (n = 10), or IA solvent injection (n = 10) as control. Treatment response was monitored by diffusion-weighted imaging and dynamic contrast enhanced-MRI obtained 1 day before and 8 days after therapy initiation. Imaging results were correlated with histopathology. In the results, IA chemotherapy showed a significant decrease in tumor volume (86.5 ± 15.6 %) compared to the IV chemotherapy (121.1 ± 39.6%) and control (126.2 ± 22.0%) 8 days after therapy (p < 0.05). Furthermore, IA chemotherapy resulted in a significant increase in mean tumor apparent diffusion coefficient (ADC) values (116.8 ± 44.9%); in contrary IV chemotherapy (66.6 ± 26.9%) and control (69.1 ± 29.5%) showed a significant decrease in ADC values corresponding to further tumor growth (p < 0.05). However, there was no significant difference in perfusion parameters including initial area under the curve, K(trans), K(ep), and V(e) between the groups (p > 0.05). Histopathology confirmed necrosis and necroptosis in the tumors after IA chemotherapy. In conclusion, IA chemotherapy may lead to effective inhibition of tumor cell proliferation and offer potential benefit of inducing higher degree of treatment response than IV chemotherapy.