TY - JOUR
T1 - Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice
AU - Verhoeff, Joost J. C.
AU - Stalpers, Lukas J. A.
AU - Coumou, Annet W.
AU - Koedooder, Kees
AU - Lavini, Cristina
AU - van Noorden, Cornelis J. F.
AU - Haveman, Jaap
AU - Vandertop, William P.
AU - van Furth, Wouter R.
PY - 2007/9/26
Y1 - 2007/9/26
N2 - BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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
AB - BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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
KW - Animals
KW - Brachytherapy/methods
KW - Brain Neoplasms/pathology
KW - Female
KW - Glioblastoma/pathology
KW - Humans
KW - Iodine Radioisotopes/administration & dosage
KW - Mice
KW - Mice, Nude
KW - Radiotherapy Dosage
KW - Survival Analysis
KW - Tumor Cells, Cultured
U2 - https://doi.org/10.1186/1748-717X-2-38
DO - https://doi.org/10.1186/1748-717X-2-38
M3 - Article
C2 - 17897452
SN - 1748-717X
VL - 2
SP - 38
JO - Radiation oncology (London, England)
JF - Radiation oncology (London, England)
IS - 1
ER -