Permeability of brain tumor vessels induced by uniform or spatially micro-fractionated synchrotron radiation therapies

Publication date: Available online 21 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Audrey Bouchet, Marine Potez, Nicolas Coquery, Claire Rome, Benjamin Lemasson, Elke Bräuer-Krisch, Chantal Rémy, Jean Laissue, Emmanuel L. Barbier, Valentin Djonov, Raphael Serduc
PurposeRadiotherapy is known to enhance permeability of brain tumor vessels. Our study compared the blood barrier permeability changes induced by synchrotron microbeam radiation therapy (MRT, which relies on spatial fractionation of the incident X-ray beam into parallel micron-wide beams) with changes induces by a spatially uniform synchrotron X-ray radiotherapy.Methods and MaterialsMale rats bearing malignant intracranial F98 gliomas were randomized into 3 groups: untreated, exposed to MRT (peak and valley dose: 241 and 10.5 Gy respectively) or exposed to broad beam irradiation (BB) delivered at comparable doses (i.e., equivalent to MRT valley dose); both applied by two arrays, intersecting orthogonally the tumor region. Vessel permeability was monitored in vivo by magnetic resonance imaging (MRI) 1 day before (T-1) and 1, 2, 7 and 14 days after treatment start. To find out whether physiological parameters influence vascular permeability, we have evaluated vessel integrity in tumor area with different values for cerebral blood flow, blood volume, oedema and tissue oxygenation.ResultsMRT does not modify the vascular permeability of normal brain tissue. MRT-induced increase of tumor vascular permeability was detectable from T2 with a maximum at T7 after exposure while BB enhanced vessel permeability only at T7. At this stage, MRT was more efficient at increasing tumor vessel permeability (BB vs untreated: +19.1%; p=0.0467; MRT vs untreated: +44.8%; p<0.0001) and its effects lasted until T14 (MRT vs BB, +22.6%; p=0.0199). We also showed that MRT was more efficient at targeting highly oxygenated (high blood volume and flow) and more proliferative parts of the tumor than BB.ConclusionsMRT-induced increased tumor vascular permeability is (i) significantly greater, (ii) earlier and more prolonged than that induced by BB irradiation, especially in highly proliferative tumor areas and (iii) targets all tumor areas discriminated by physiological characteristics, including those not damaged by homogeneous irradiation.

Teaser

Synchrotron microbeam radiation therapy (MRT), based on spatial fractionation of the incident beam, is more efficient than broad beam irradiation (BB) at opening the blood-brain barrier of intracranial rodent glioblastomas. MRT-induced increased tumor vascular permeability is (i) significantly greater, (ii) earlier and more prolonged than that induced by BB irradiation, especially in highly proliferative tumor areas and (iii) targets all tumor areas discriminated by physiological characteristics, including those not damaged by homogeneous irradiation.


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