In:
Acta Radiologica, SAGE Publications, Vol. 56, No. 3 ( 2015-03), p. 294-303
Abstract:
Novel anti-angiogenic treatments are increasingly complementing established cancer therapy strategies in head and neck tumors. Contrast-enhanced magnetic resonance imaging (MRI) can be applied for early and non-invasive therapy monitoring by non-invasive quantitative assessment of tumor microcirculation as in vivo imaging biomarkers of therapy response. Purpose To monitor the anti-angiogenic effects of a novel combination therapy on experimental head and neck squamous cell carcinomas (HNSCC) with dynamic contrast-enhanced (DCE)-MRI. Material and Methods Athymic rats ( n = 18) with subcutaneous HNSCC xenografts were investigated by DCE-MRI before and after 7 days of a daily triple therapy regimen combining the COX-II-inhibitor celecoxib, the matrix-metalloproteinase-inhibitor GM6001, and the uPA-inhibitor upamostat. Quantitative measurements of tumor blood flow (tBF), tumor blood volume (tBV), and permeability-surface area product (PS) were calculated and validated by immunohistochemistry. Results Mean tBF and tBV in triple-therapy animals decreased significantly from day 0 to day 7 (tBF, 41.0 ± 14.2 to 20.4 ± 5.7 mL/100 mL/min; P 〈 0.01; tBV, 17.7 ± 3.9 to 7.5 ± 3.3%; P 〈 0.01). No significant effects on PS were observed in either group ( P 〉 0.05). Immunohistochemical analysis showed a significantly lower tumor vascularity in the therapy group than in the control group (CD31), significantly fewer Ki-67+ proliferating tumor cells and significantly more Capase-3+ apoptotic tumor cells ( P 〈 0.05). Significant ( P 〈 0.05) correlations were observed between tBF/tBV and CD31 (tBF, r = 0.84; tBV, r = 0.70), tBV and Ki-67 (r = 0.62), as well as tBF and caspase-3 (r = −0.64). Conclusion DCE-MRI may be a suitable tool for the non-invasive monitoring of the anti-vascular effects of this innovative triple therapy regimen with potential for clinical translation.
Type of Medium:
Online Resource
ISSN:
0284-1851
,
1600-0455
DOI:
10.1177/0284185114527444
Language:
English
Publisher:
SAGE Publications
Publication Date:
2015
detail.hit.zdb_id:
105-3
detail.hit.zdb_id:
2024579-8
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