Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy

Abstract

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

“…Some pre-clinical trials note the development of minor cerebral oedemas following MRT [18]. However, the oedemas disappear within a week after the MRT treatment, in agreement with studies that highlight the success of normal tissue sparing with MRT [9][10][11][12][13][14][15][16][17].…”

“…With a selective internalisation in the tumour cells, higher target doses may be delivered to the tumour, which is beneficial for effective treatment of radioresistant cancers [5,16,17].…”

“…The key advantage of MRT arises from the reported increase in sensitivity of tumour tissue to the microbeam array, which differs to the observed recovery of normal tissue [9][10][11][12][13][14][15][16][17]. Radiation treatments for radioresistant tumours such as gliomas, require extremely high absorbed doses [15,16], yet with their development in sensitive brain tissue, large doses cannot be administered without significant damage.…”

“…Radiation treatments for radioresistant tumours such as gliomas, require extremely high absorbed doses [15,16], yet with their development in sensitive brain tissue, large doses cannot be administered without significant damage.…”

“…Radioresistant brain tumours, such as 9L gliosarcoma, are seen to be more effectively treated with MRT than broad beams due to large peak doses [15,16]. Crosbie et al [11], indicates that there is a significant difference in the migration of tumour cells in comparison to the normal cells.…”