Spatially fractionated minibeam radiation delivered at clinically feasible dose rates induces transient vascular permeability

Microbeam Radiation Therapy is a preclinical form of spatially fractionated radiation therapy that utilizes synchrotron X-rays to deliver highly heterogeneous dose distributions at a micrometric scale. This radiation scheme has been shown to facilitate the induction of controlled and reversible vascular permeability, enhancing treatment efficacy of systemic therapeutic agents. Despite the promising preclinical results, translating microbeam SFRT to the clinic has been hindered by a reliance on synchrotron sources that operate at dose rates orders of magnitude greater than what is possible with clinical machines. Without rapid dose delivery, the microbeam geometry is susceptible to blurring due to physiologic motion when delivered at clinical dose rates. Therefore, larger beam widths, spaced further apart (minibeams) were employed to determine whether such effects can be observed with clinically achievable doses and dose rates. Vascular permeability was assessed in the chick chorioallantoic membrane vasculature following minibeam irradiation delivered at peak doses (10 Gy) and dose rates (10 Gy/s and 0.05 Gy/s) approaching clinical relevance. Transient, reversible permeability could be induced at these dose rates beginning 1–2 h post-irradiation. This was followed by temporary vascular occlusion in the beam path that was resolved by 7 h when delivered at 10 Gy/s but persisted longer when delivered at 0.05 Gy/s. Despite these changes, vascular function was maintained at both dose rates by 24 h post-IR, differing only in the degree of regeneration. The induction of permeability was also maintained when using a clinical orthovoltage system further supporting the potential clinical application of minibeam radiation therapy.