Sterzik Alexander, Paprottka Philipp M, Zengel Pamela, Hirner Heidrun, Roßpunt Svenja, Eschbach Ralf, Moser Matthias, Havla Lukas, Ingrisch Michael, Mack Brigitte, Reiser Maximilian F, Nikolaou Konstantin, Cyran Clemens C
Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany.
Acta Radiol. 2015 Mar;56(3):294-303. doi: 10.1177/0284185114527444. Epub 2014 Mar 7.
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.
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.
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.
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).
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.
新型抗血管生成疗法在头颈部肿瘤的既定癌症治疗策略中发挥着越来越重要的补充作用。对比增强磁共振成像（MRI）可通过对肿瘤微循环进行非侵入性定量评估，作为治疗反应的体内成像生物标志物，用于早期和非侵入性治疗监测。
利用动态对比增强（DCE）-MRI监测一种新型联合疗法对实验性头颈部鳞状细胞癌（HNSCC）的抗血管生成作用。
对18只皮下接种HNSCC异种移植物的无胸腺大鼠，在每日联合使用COX-II抑制剂塞来昔布、基质金属蛋白酶抑制剂GM6001和尿激酶型纤溶酶原激活物抑制剂乌帕司他进行三联疗法7天前后，采用DCE-MRI进行研究。计算肿瘤血流量（tBF）、肿瘤血容量（tBV）和通透表面积乘积（PS）的定量测量值，并通过免疫组织化学进行验证。
三联疗法组动物的平均tBF和tBV从第0天到第7天显著降低（tBF，41.0±14.2至20.4±5.7 mL/100 mL/min；P<0.01；tBV，17.7±3.9至7.5±3.3%；P<0.01）。两组对PS均未观察到显著影响（P>0.05）。免疫组织化学分析显示，治疗组的肿瘤血管生成明显低于对照组（CD31），Ki-67+增殖肿瘤细胞明显减少，Caspase-3+凋亡肿瘤细胞明显增多（P<0.05）。观察到tBF/tBV与CD31（tBF，r=0.84；tBV，r=0.70）、tBV与Ki-67（r=0.62）以及tBF与Caspase-3（r=-0.64）之间存在显著（P<0.05）相关性。
DCE-MRI可能是一种适用于非侵入性监测这种创新三联疗法抗血管作用的工具，具有临床转化潜力。
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