Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT)

Abstract

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25-75 micron-wide microplanar beams separated by wider (100-400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified. SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.

A preclinical microbeam facility with a conventional x‐ray tube

“…With the presented setup, dose rates of up to 300 mGy/s were reached at a beam width of 50 μ m and a beam‐to‐beam spacing of 400 μ m. Beam‐to‐beam spacing and beam width correspond to the specifications envisaged for future clinical trials at the European Synchrotron (ESRF) in Grenoble 27 . Dose rates for MRT at the European Synchrotron reach between 8 and 16 kGy/s 25 and are orders of magnitude higher than at an x‐ray tube. However, the synchrotron beam at the ESRF has a maximum height of just 520 μ m. Therefore the target has to be scanned through the beam to produce higher fields, while the x‐ray tube produced microbeam field can be applied statically.…”

“…The exposure was chosen such that peak doses are at 80 Gy. Technical details of MRT exposures at the ESRF can, for example, be found in Bräuer‐Krisch et al 25 …”

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

“…MRT involves the application of an array of spatially fractionated microbeams sourced from third generation synchrotrons, with beam widths ranging from 25 to 75 µm, and a pitch of 200-400 µm [2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

“…Microbeam peak doses of between 500-1000 Gy can be delivered safely due to the wellknown dose volume effect [5][6][7][8].…”

“…Small PVDRs indicate that the valley dose between adjacent microbeams, is large in relation to the peak dose. When made comparable to the large peak doses, this indicates better tumour coverage [7,8]. Conversely, a large PVDR and small valley dose may be more accommodating for tissue recovery, allowing normal tissue to be spared through the dose-volume effect [5][6][7][8].…”