Abstract
We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.
Highlights
The high photon flux of synchrotron-generated X-rays allows the design of radiotherapeutic approaches that could not be executed with the radiotherapy equipment presently available in the hospital environment
In one single Microbeam radiation therapy (MRT) irradiation session it is possible to apply radiation doses that are higher by at least one order of magnitude, compared to the total radiation dose commonly applied during a complete cycle of temporally fractionated radiotherapy for malignant brain tumors in the hospital setting
It has been shown that the overall structure of the healthy tissue between the paths of the microbeams stays intact [2] and that the function of healthy tissue in the path of the beam is greatly preserved after MRT, possibly taking over part of the function of the tissue destroyed in the path of the microbeams [3,4]
Summary
The high photon flux of synchrotron-generated X-rays allows the design of radiotherapeutic approaches that could not be executed with the radiotherapy equipment presently available in the hospital environment. Microbeam radiation therapy (MRT) is a synchrotron-based experimental concept of spatially fractionated radiotherapy. In one single MRT irradiation session it is possible to apply radiation doses that are higher by at least one order of magnitude, compared to the total radiation dose commonly applied during a complete cycle of temporally fractionated radiotherapy for malignant brain tumors in the hospital setting. Characteristic for microbeam radiotherapy is the application of a spatially fractionated high dose of X-rays generated by a special collimator [1]. The application of high irradiation doses should prove an advantage in the work with highly radioresistant tumors. It has been shown previously that microbeam radiation therapy significantly increases survival time in animal models of malignant brain tumor [2,3,5,6,7,8].
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