Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice.
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.


CONCLUSIONS
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.
Verhoeff
Joost J C
JJ
Department of Neurosurgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. j.j.verhoeff@amc.uva.nl
Stalpers
Lukas J A
LJ
Coumou
Annet W
AW
Koedooder
Kees
K
Lavini
Cristina
C
Van Noorden
Cornelis J F
CJ
Haveman
Jaap
J
Vandertop
William P
WP
van Furth
Wouter R
WR
D000818:Animals; D001918:Brachytherapy / Q000379:methods*; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes