Université Grenoble Alpes, Institut National de la Santé et de la Recherche Médicale UA7 Synchrotron Radiation for Biomedicine, Saint-Martin d'Hères, France.
Centre Hospitalier Universitaire Grenoble Alpes, Maquis du Grésivaudan, La Tronche, France.
Int J Radiat Oncol Biol Phys. 2024 Sep 1;120(1):178-188. doi: 10.1016/j.ijrobp.2024.02.053. Epub 2024 Mar 8.
Novel radiation therapy approaches have increased the therapeutic efficacy for malignant brain tumors over the past decades, but the balance between therapeutic gain and radiotoxicity remains a medical hardship. Synchrotron microbeam radiation therapy, an innovative technique, deposes extremely high (peak) doses in micron-wide, parallel microbeam paths, whereas the diffusing interbeam (valley) doses lie in the range of conventional radiation therapy doses. In this study, we evaluated normal tissue toxicity of whole-brain microbeam irradiation (MBI) versus that of a conventional hospital broad beam (hBB).
Normal Fischer rats (n = 6-7/group) were irradiated with one of the two modalities, exposing the entire brain to MBI valley/peak doses of 0/0, 5/200, 10/400, 13/520, 17/680, or 25/1000 Gy or to hBB doses of 7, 10, 13, 17, or 25 Gy. Two additional groups of rats received an MBI valley dose of 10 Gy coupled with an hBB dose of 7 or 15 Gy (groups MBI17* and MBI25*). Behavioral parameters were evaluated for 10 months after irradiation combined with veterinary observations.
MBI peak doses of ≥680 Gy caused acute toxicity and death. Animals exposed to hBB or MBI dose-dependently gained less weight than controls; rats in the hBB25 and MBI25* groups died within 6 months after irradiation. Increasing doses of MBI caused hyperactivity but no other detectable behavioral alterations in our tests. Importantly, no health concerns were seen up to an MBI valley dose of 17 Gy.
While acute toxicity of microbeam exposures depends on very high peak doses, late toxicity mainly relates to delivery of high MBI valley doses. MBI seems to have a low impact on normal rat behavior, but further tests are warranted to fully explore this hypothesis. However, high peak and valley doses are well tolerated from a veterinary point of view. This normal tissue tolerance to whole-brain, high-dose MBI reveals a promising avenue for microbeam radiation therapy, that is, therapeutic applications of microbeams that are poised for translation to a clinical environment.
在过去几十年中，新型放射治疗方法提高了恶性脑肿瘤的治疗效果，但治疗增益与放射性毒性之间的平衡仍是医学难题。同步微束放射治疗是一种创新技术，它在微米宽的平行微束路径中沉积极高（峰值）剂量，而扩散的束间（谷值）剂量处于常规放射治疗剂量范围内。在这项研究中，我们评估了全脑微束照射（MBI）与常规医院宽束（hBB）的正常组织毒性。
正常的 Fischer 大鼠（每组 6-7 只）接受其中一种治疗方式照射，使整个大脑接受 MBI 谷值/峰值剂量为 0/0、5/200、10/400、13/520、17/680 或 25/1000 Gy，或 hBB 剂量为 7、10、13、17 或 25 Gy。另外两组大鼠接受 MBI 谷值剂量 10 Gy 并结合 hBB 剂量 7 或 15 Gy（MBI17和 MBI25组）。照射后结合兽医观察，对行为参数进行了 10 个月的评估。
MBI 峰值剂量≥680 Gy 引起急性毒性和死亡。接受 hBB 或 MBI 照射的大鼠体重比对照组减轻；照射后 6 个月内 hBB25 和 MBI25*组的大鼠死亡。MBI 剂量依赖性地增加导致大鼠过度活跃，但在我们的测试中没有发现其他可检测到的行为改变。重要的是，直到 MBI 谷值剂量为 17 Gy 才出现健康问题。
虽然微束照射的急性毒性取决于非常高的峰值剂量，但迟发性毒性主要与高 MBI 谷值剂量有关。MBI 似乎对正常大鼠行为影响较小，但需要进一步测试来充分验证这一假设。然而，从兽医角度来看，高峰值和谷值剂量是可以耐受的。全脑高剂量 MBI 的这种正常组织耐受性为微束放射治疗开辟了一条有希望的途径，即微束治疗的应用有望转化为临床环境。
