Verhoeff Joost J C, Stalpers Lukas J A, Coumou Annet W, Koedooder Kees, Lavini Cristina, Van Noorden Cornelis J F, Haveman Jaap, Vandertop William P, van Furth Wouter R
Department of Neurosurgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Radiat Oncol. 2007 Sep 26;2:38. doi: 10.1186/1748-717X-2-38.
High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models- high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors.
Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 x 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy).
In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals.
The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy- without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.
高剂量放疗是脑癌患者的标准治疗方法。然而，在临床前研究中，外照射放疗仅限于异位小鼠模型——由于辐射毒性，对小鼠头部进行高剂量放疗是致命的。因此，我们开发了一种立体定向近距离放疗小鼠模型，用于对实验性脑内（原位）脑肿瘤进行高剂量局部照射。
21只裸鼠在颅骨中植入空心导向螺钉。三周后，注射5×10⁵个U251-NG2人胶质母细胞瘤细胞。五天后，在11只随机选择的小鼠中通过导向螺钉插入一枚2毫居里的碘-125近距离放疗籽源；10只小鼠接受假籽源。当出现严重的神经或身体症状时，对小鼠实施安乐死。13周后，活性碘-125籽源下方5毫米处的累积照射剂量为23.0 Gy（肿瘤等效生物剂量=30.6 Gy）。
在假手术组中，10只动物中有9只（90%）在6周内出现致命性肿瘤进展迹象。在实验组中，11只小鼠中有2只（18%）在13周内死于肿瘤进展。在接受照射的动物中未观察到体重减轻或神经症状等急性副作用。
通过立体定向导向螺钉在植入脑肿瘤的小鼠颅骨内植入碘-125近距离放疗籽源，可显著延长生存期，这是由于对脑肿瘤进行了高剂量照射，其生物学效应与高剂量分割放疗相当，且无致命的辐射毒性。这是一种用于测试原位脑肿瘤治疗与放射治疗联合应用的优秀小鼠模型。
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