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用于原位胰腺肿瘤小鼠模型高精度放疗的生物标记物:液体基准标记物的应用经验

BioXmark for high-precision radiotherapy in an orthotopic pancreatic tumor mouse model : Experiences with a liquid fiducial marker.

作者信息

Dobiasch S, Kampfer S, Burkhardt R, Schilling D, Schmid T E, Wilkens J J, Combs S E

机构信息

Department of Radiation Oncology, Technical University of Munich (TUM), Klinikum rechts der Isar, Ismaninger Straße 22, 81675, Munich, Germany.

Partner Site Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Munich, Germany.

出版信息

Strahlenther Onkol. 2017 Dec;193(12):1039-1047. doi: 10.1007/s00066-017-1193-y. Epub 2017 Aug 14.

Abstract

BACKGROUND AND PURPOSE

High-precision radiotherapy (RT) requires precise positioning, particularly with high single doses. Fiducial markers in combination with onboard imaging are excellent tools to support this. The purpose of this study is to establish a pancreatic cancer mouse model for high-precision image-guided RT (IGRT) using the liquid fiducial marker BioXmark (Nanovi, Kongens Lyngby, Denmark).

METHODS

In an animal-based cancer model, different volumes of BioXmark (10-50 µl), application forms, and imaging modalities-cone-beam computer tomography (CBCT) incorporated in either the Small Animal Radiation Research Platform (SARRP) or the small-animal micro-CT Scanner (SkyScan; Bruker, Brussels, Belgium)-as well as subsequent RT with the SARRP system were analyzed to derive recommendations for BioXmark.

RESULTS

Even small volumes (10 µl) of BioXmark could be detected by CBCT (SARRP and Skyscan). Larger volumes (50 µl) led to hardening artefacts. The position of BioXmark was monitored at least weekly by CBCT and was stable over 4 months. BioXmark was shown to be well tolerated; no changes in physical condition or toxic side effects were observed in comparison to control mice. BioXmark enabled an exact fusion with the original treatment plan with less hardening artefacts, and minimized the application of contrast agent for fractionated RT.

CONCLUSION

An orthotopic pancreatic tumor mouse model was established for high-precision IGRT using a fiducial marker. BioXmark was successfully tested and provides the perfect basis for improved imaging in high-precision RT. BioXmark enables a unique application method and optimal targeted precision in fractionated RT. Therefore, preclinical trials evaluating novel fractionation regimens and/or combination treatment with high-end RT can be performed.

摘要

背景与目的

高精度放射治疗(RT)需要精确的定位,尤其是高单次剂量照射时。基准标记物与机载成像相结合是实现这一目标的优秀工具。本研究的目的是使用液体基准标记物BioXmark(丹麦哥本哈根林比市Nanovi公司)建立一种用于高精度图像引导放射治疗(IGRT)的胰腺癌小鼠模型。

方法

在基于动物的癌症模型中,分析了不同体积(10 - 50微升)的BioXmark、应用形式、成像方式——结合在小动物放射研究平台(SARRP)或小动物微型CT扫描仪(SkyScan;比利时布鲁塞尔布鲁克公司)中的锥形束计算机断层扫描(CBCT)——以及随后使用SARRP系统进行的放射治疗,以得出关于BioXmark的建议。

结果

CBCT(SARRP和SkyScan)能够检测到即使是小体积(10微升)的BioXmark。较大体积(50微升)会导致硬化伪影。通过CBCT至少每周监测一次BioXmark的位置,其在4个月内保持稳定。结果表明BioXmark耐受性良好;与对照小鼠相比,未观察到身体状况变化或毒性副作用。BioXmark能够实现与原始治疗计划的精确融合,硬化伪影较少,并最大限度地减少了分次放射治疗中造影剂的使用。

结论

使用基准标记物建立了一种用于高精度IGRT的原位胰腺肿瘤小鼠模型。BioXmark已成功测试,并为高精度放射治疗中改进成像提供了理想基础。BioXmark在分次放射治疗中实现了独特的应用方法和最佳靶向精度。因此,可以开展评估新型分割方案和/或与高端放射治疗联合治疗的临床前试验。

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