5 years ago

Minibeam radiotherapy with small animal irradiators; <i>in-vitro</i> and <i>in-vivo</i> feasibility studies.

Zhou, Lee, O'Brien Iii, Inscoe, Bazyar
Minibeam radiation therapy (MBRT) delivers ultrahigh dose of X-ray (≥100 Gy) in 200-1000 μm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of present study was to develop an efficient and accessible method to perform MBRT using a conventional X-ray irradiator. We then tested this new method both in-vitro and in-vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converts the cone beam of an industrial irradiator to 44 identical beams (Collimator size ≈ 4×10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM = 246±32 μm; center-to-center = 926±23 μm; peak-to-valley dose ratio = 24.35±2.10; collimator relative output factor = 0.84±0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP = glioblastoma; B16-F10 = melanoma). Radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). The normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumor compared to CRT when RBE were applied (overall p<.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in-vivo (mouse brain tissue) and up to 10cm deep in the radiochromic film. In conclusion, the initial dosimetric, in-vitro and in-vivo evaluations confirmed the utility of this affordable and easy-to-replicate minibeam collimator for future preclinical studies.

Publisher URL: http://doi.org/10.1088/1361-6560/aa926b

DOI: 10.1088/1361-6560/aa926b

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