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原位头颈癌小鼠模型的多模态成像分析及抗CD137肿瘤免疫治疗的应用

Multimodal imaging analysis of an orthotopic head and neck cancer mouse model and application of anti-CD137 tumor immune therapy.

作者信息

Vahle Anne-Kristin, Hermann Sven, Schäfers Michael, Wildner Michael, Kerem Alexander, Öztürk Ender, Jure-Kunkel Maria, Franklin Cindy, Lang Stephan, Brandau Sven

机构信息

Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.

European Institute for Molecular Imaging, University of Münster, Münster, Germany.

出版信息

Head Neck. 2016 Apr;38(4):542-9. doi: 10.1002/hed.23929. Epub 2015 Jun 16.

DOI:10.1002/hed.23929
PMID:25482887
Abstract

BACKGROUND

Recent technical progress makes sophisticated noninvasive imaging methods available for murine models. For the first time, in this study, we applied fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT and FDG-PET-MRI to a murine orthotopic model of head and neck cancer immunotherapy.

METHODS

Tumor growth of floor of the mouth tumors was evaluated by multimodal small-animal imaging using FDG-PET-CT and FDG-PET-MRI. The immunotherapeutic effects of anti-CD137 antibody therapy were examined on body weight, tumor growth, and tumor-infiltrating immune cells in longitudinal imaging studies and immunohistochemical analyses.

RESULTS

Imaging revealed aggressive, fast-growing tumors without evidence of local or distant metastases. CD137 immunotherapy decreased tumor take and growth and stabilized body weight over time. A clear case of tumor regression was demonstrated by longitudinal PET-CT.

CONCLUSION

The murine model mimics the characteristics of head and neck cancer in humans and offers excellent opportunities to investigate immunomodulatory anticancer drugs. The CD137 antibody showed antitumor effects in some therapy-responsive mice.

摘要

背景

近期的技术进步使得复杂的非侵入性成像方法可用于小鼠模型。在本研究中,我们首次将氟脱氧葡萄糖(FDG)正电子发射断层扫描(PET)-CT和FDG-PET-MRI应用于头颈癌免疫治疗的小鼠原位模型。

方法

通过使用FDG-PET-CT和FDG-PET-MRI的多模态小动物成像评估口腔底部肿瘤的生长情况。在纵向成像研究和免疫组织化学分析中,检测抗CD137抗体疗法对体重、肿瘤生长和肿瘤浸润免疫细胞的免疫治疗效果。

结果

成像显示肿瘤具有侵袭性、生长迅速,且无局部或远处转移的迹象。随着时间的推移,CD137免疫疗法降低了肿瘤的发生率和生长速度,并稳定了体重。纵向PET-CT显示了一例明显的肿瘤消退病例。

结论

该小鼠模型模拟了人类头颈癌的特征,为研究免疫调节抗癌药物提供了绝佳机会。CD137抗体在一些对治疗有反应的小鼠中显示出抗肿瘤作用。

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