Medical Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):514-9. doi: 10.1016/j.ijrobp.2011.12.025. Epub 2012 Feb 17.
To evaluate the efficacy of "interleaved carbon minibeams" for ablating a 6.5-mm target in a rabbit brain with little damage to the surrounding brain. The method is based on the well-established tissue-sparing effect of arrays of thin planes of radiation.
Broad carbon beams from the National Aeronautics and Space Agency Space Radiation Facility at Brookhaven National Laboratory were segmented into arrays of parallel, horizontal, 0.3-mm-thick planar beams (minibeams). The minibeams' gradual broadening in tissues resulted in 0.525-mm beam thickness at the target's proximal side in the spread-out Bragg peak. Interleaving was therefore implemented by choosing a 1.05 mm beam spacing on-center. The anesthetized rabbit, positioned vertically on a stage capable of rotating about a vertical axis, was exposed to arrays from four 90° angles, with the stage moving up by 0.525 mm in between. This produced a solid radiation field at the target while exposing the nontargeted tissues to single minibeam arrays. The target "physical" absorbed dose was 40.2 Gy.
The rabbit behaved normally during the 6-month observation period. Contrast magnetic resonance imaging and hematoxylin and eosin histology at 6 months showed substantial focal target damage with little damage to the surrounding brain.
We plan to evaluate the method's therapeutic efficacy by comparing it with broad-beam carbon therapy in animal models. The method's merits would combine those of carbon therapy (i.e., tight target dose because of the carbon's Bragg-peak, sharp dose falloff, and high relative biological effectiveness at the target), together with the method's low impact on the nontargeted tissues. The method's smaller impact on the nontargeted brain might allow carbon therapy at higher target doses and/or lower normal tissue impact, thus leading to a more effective treatment of radioresistant tumors. It should also make the method more amenable to administration in either a single dose fraction or in a small number of fractions.
评估“交错碳微束”消融 6.5mm 兔脑目标的疗效，同时尽量减少对周围脑组织的损伤。该方法基于已确立的薄射线平面阵列的组织保护效应。
来自布鲁克海文国家实验室美国国家航空航天局太空辐射设施的宽碳束被分割成平行的、水平的、0.3mm 厚的平面束（微束）阵列。微束在组织中的逐渐变宽导致在展宽布拉格峰的近端目标侧达到 0.525mm 的束厚。因此，通过选择中心距 1.05mm 的交错实现交错。麻醉的兔子垂直放置在一个能够绕垂直轴旋转的台上，从四个 90°角暴露在阵列中，在两个角之间台上升 0.525mm。这在目标处产生了一个实心辐射场，同时使非目标组织暴露在单个微束阵列中。目标“物理”吸收剂量为 40.2Gy。
兔子在 6 个月的观察期内表现正常。6 个月时的对比磁共振成像和苏木精和伊红组织学显示，目标有大量的局灶性损伤，而周围脑组织的损伤很小。
我们计划通过在动物模型中比较该方法与宽束碳治疗来评估该方法的治疗效果。该方法的优点将结合碳治疗的优点（即由于碳的布拉格峰，目标处的紧束剂量，陡峭的剂量下降，以及目标处的高相对生物学效应），以及对非目标组织的低影响。该方法对非目标脑的影响较小可能允许在更高的目标剂量和/或更低的正常组织影响下进行碳治疗，从而使放射性抵抗肿瘤的治疗更有效。它还应该使该方法更适合单次剂量或少数剂量的给药。
