Bouchet Audrey, Potez Marine, Coquery Nicolas, Rome Claire, Lemasson Benjamin, Bräuer-Krisch Elke, Rémy Chantal, Laissue Jean, Barbier Emmanuel L, Djonov Valentin, Serduc Raphael
Group Topographic and Clinical Anatomy, Institute of Anatomy, University of Bern, Bern, Switzerland.
Rayonnement synchrotron et Recherche médicale, Université Grenoble Alpes, Grenoble, France.
Int J Radiat Oncol Biol Phys. 2017 Aug 1;98(5):1174-1182. doi: 10.1016/j.ijrobp.2017.03.025. Epub 2017 Mar 21.
To compare the blood-brain 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 induced by a spatially uniform synchrotron x-ray radiation therapy.
Male 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 (ie, equivalent to MRT valley dose); both applied by 2 arrays, intersecting orthogonally the tumor region. Vessel permeability was monitored in vivo by magnetic resonance imaging 1 day before (T) and 1, 2, 7, and 14 days after treatment start. To determine whether physiologic parameters influence vascular permeability, we evaluated vessel integrity in the tumor area with different values for cerebral blood flow, blood volume, edema, and tissue oxygenation.
Microbeam radiation therapy does not modify the vascular permeability of normal brain tissue. Microbeam radiation therapy-induced increase of tumor vascular permeability was detectable from T with a maximum at T after exposure, whereas BB enhanced vessel permeability only at T. At this stage MRT was more efficient at increasing tumor vessel permeability (BB vs untreated: +19.1%; P=.0467; MRT vs untreated: +44.8%; P<.0001), and its effects lasted until T (MRT vs BB, +22.6%; P=.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.
Microbeam radiation therapy-induced increased tumor vascular permeability is: (1) significantly greater; (2) earlier and more prolonged than that induced by BB irradiation, especially in highly proliferative tumor areas; and (3) targets all tumor areas discriminated by physiologic characteristics, including those not damaged by homogeneous irradiation.
比较同步加速器微束放射治疗（MRT，其依赖于将入射X射线束空间分割为平行的微米级宽光束）与空间均匀的同步加速器X射线放射治疗所引起的血脑屏障通透性变化。
将患有恶性颅内F98胶质瘤的雄性大鼠随机分为3组：未治疗组、接受MRT治疗组（峰值和谷值剂量分别为241和10.5 Gy）或接受剂量相当的宽束照射（BB）组（即相当于MRT谷值剂量）；两者均通过2个阵列施加，正交穿过肿瘤区域。在治疗开始前1天（T）以及治疗开始后1、2、7和14天，通过磁共振成像在体内监测血管通透性。为了确定生理参数是否影响血管通透性，我们评估了肿瘤区域具有不同脑血流量、血容量、水肿和组织氧合值的血管完整性。
微束放射治疗不会改变正常脑组织的血管通透性。微束放射治疗引起的肿瘤血管通透性增加在T时即可检测到，照射后在T时达到最大值，而BB仅在T时增强血管通透性。在此阶段，MRT在增加肿瘤血管通透性方面更有效（BB与未治疗组相比：增加19.1%；P = 0.0467；MRT与未治疗组相比：增加44.8%；P < 0.0001），并且其效果持续到T（MRT与BB相比，增加22.6%；P = 0.0199）。我们还表明，与BB相比，MRT在靶向肿瘤中高氧合（高血容量和血流）且增殖性更强的部分方面更有效。
微束放射治疗引起的肿瘤血管通透性增加：（1）显著更大；（2）比BB照射更早且持续时间更长，尤其是在增殖性高的肿瘤区域；（3）靶向所有根据生理特征区分的肿瘤区域，包括那些未受均匀照射损伤的区域。
