Evaluation of metronomic chemotherapy response using diffusion and dynamic contrast-enhanced MRI. PLoS One 2020;15(11):e0241916
Date
11/26/2020Pubmed ID
33237905Pubmed Central ID
PMC7688103DOI
10.1371/journal.pone.0241916Scopus ID
2-s2.0-85096818213 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
PURPOSE: To investigate the feasibility of using diffusion MRI (dMRI) and dynamic contrast-enhanced (DCE) MRI to evaluate the treatment response of metronomic chemotherapy (MCT) in the 4T1 mammary tumor model of locally advanced breast cancer.
METHODS: Twelve Balb/c mice with metastatic breast cancer were divided into treated and untreated (control) groups. The treated group (n = 6) received five treatments of anti-metabolite agent 5-Fluorouracil (5FU) in the span of two weeks. dMRI and DCE-MRI were acquired for both treated and control groups before and after MCT. Immunohistochemically staining and measurements were performed after the post-MRI measurements for comparison.
RESULTS: The control mice had significantly (p<0.005) larger tumors than the MCT treated mice. The DCE-MRI analysis showed a decrease in contrast enhancement for the control group, whereas the MCT mice had a more stable enhancement between the pre-chemo and post-chemo time points. This confirms the antiangiogenic effects of 5FU treatment. Comparing amplitude of enhancement revealed a significantly (p<0.05) higher enhancement in the MCT tumors than in the controls. Moreover, the MCT uptake rate was significantly (p<0.001) slower than the controls. dMRI analysis showed the MCT ADC values were significantly larger than the control group at the post-scan time point.
CONCLUSION: dMRI and DCE-MRI can be used as potential biomarkers for assessing the treatment response of MCT. The MRI and pathology observations suggested that in addition to the cytotoxic effect of cell kills, the MCT with a cytotoxic drug, 5FU, induced changes in the tumor vasculature similar to the anti-angiogenic effect.
Author List
Baboli M, Winters KV, Freed M, Zhang J, Kim SGAuthor
Mehran Baboli PhD Assistant Professor in the Radiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Administration, MetronomicAnimals
Antimetabolites, Antineoplastic
Case-Control Studies
Contrast Media
Diffusion Magnetic Resonance Imaging
Feasibility Studies
Female
Fluorouracil
Longitudinal Studies
Magnetic Resonance Imaging
Mammary Neoplasms, Animal
Mice
Mice, Inbred BALB C
Neoplasm Metastasis
Treatment Outcome
