ABSTRACT
The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium-7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of planar parallel minibeams having 300-micron width and 1-mm center-to-center spacing within a circular array. We followed animals for 6 months after treatment and utilized behavioral testing and immunohistochemical studies to investigate the resulting cognitive impairment and chronic pathologic changes. We found both solid-beam therapy and minibeam therapy to result in cognitive impairment compared with sham controls, with no apparent reduction in neurotoxicity using heavy ion minibeams instead of solid beams under the conditions of this study.
ABSTRACT
AIM: To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. MATERIALS & METHODS: Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. RESULTS: Gold uptake gave a 19:1 tumor to normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. CONCLUSION: Intravenously injected gold nanoparticles cross the blood-tumor barrier, but are largely blocked by the normal blood-brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers.