Halperin E C, Samulski T, Oakes W J, Friedman H S
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
J Neurooncol. 1996 Jan;27(1):39-46. doi: 10.1007/BF00146082.
PURPOSE/OBJECTIVE: Some malignant brain tumors shed cells into the cerebrospinal fluid (CSF). These tumors may implant throughout the neuroaxis via the CSF. With the placement of a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt, tumor cells free-floating in the CSF may be carried through the shunt to the remainder of the body. Mechanical filtration devices to prevent this are not reliable. We report the development of a new device capable of reducing the incidence of shunt promoted metastasis.
MATERIALS & METHODS: The device exposes the draining CSF, as it passes through a baffle system, to a localized high-intensity radiation field adequately shielded from surrounding normal tissue. The prototype consists of geometrically fixed iodine-125 (125I) sources. The device accommodates the maximum CSF flow rate of 500 ml/24 hours. Radiation exposure to clonogenic cells occurs as they transit through the baffle system. Since the volume of the prototype device is 14 ml, a tumor cell floating through the device will be exposed to radiation for 40 minutes. Utilizing the human medulloblastoma cell line D425 MED, a limiting dilution clonogenic assay was performed. Suspensions of tumor cells in liquid medium were pumped through the device at the maximum anticipated CSF production rate of 0.35 ml/min. After the cells, with their tissue culture medium, were received from the device, a series of nine 5-fold dilutions were prepared from the suspensions which initially contained 10(6) tumor cell/ml. Plates were then incubated and growth was demonstrated by visual scoring of colonies of more than 20 cells. Limiting dilution data analysis was performed. Radiation surveys of the fully loaded (approximately 1.8 Ci) 125I prototype were conducted. A well calibrator was used to measure the activity of the fully loaded device.
When the device was loaded with 125I seeds providing a dose of 364-479 cGy the probability of clonogen survival was 0.033. Radiation exposure levels at the exterior surface of the shielded device were in the range of 2-5 mR/hr and thus fell within guidelines for acceptable normal tissue exposure. Attenuation of radiation by the shielding case for the fully loaded device was 10(-5).
The device kills medulloblastoma cells as they are pumped through it. If the risk of metastasis is linearly related to the number of clonogenic cells, then the device would, we infer, reduce the risk of shunt-born metastasis by a factor of 0.033 and merits further investigation.
目的/目标：一些恶性脑肿瘤会向脑脊液（CSF）中释放细胞。这些肿瘤可能会通过脑脊液在整个神经轴上着床。随着脑室腹腔（VP）或脑室心房（VA）分流器的置入，脑脊液中游离的肿瘤细胞可能会通过分流器被带到身体的其他部位。用于防止这种情况的机械过滤装置并不可靠。我们报告了一种能够降低分流促进转移发生率的新装置的研发情况。
该装置在引流的脑脊液通过挡板系统时，将其暴露于一个局部高强度辐射场中，该辐射场对周围正常组织有充分的屏蔽。原型由几何形状固定的碘-125（125I）源组成。该装置可适应最大脑脊液流速为500 ml/24小时。当克隆形成细胞通过挡板系统时会受到辐射暴露。由于原型装置的体积为14 ml，一个漂浮通过该装置的肿瘤细胞将受到40分钟的辐射。利用人髓母细胞瘤细胞系D425 MED进行了有限稀释克隆形成试验。将肿瘤细胞在液体培养基中的悬浮液以预期的最大脑脊液产生速率0.35 ml/min泵入该装置。在细胞及其组织培养基从该装置流出后，从最初含有10(6)个肿瘤细胞/ml的悬浮液中制备一系列9个5倍稀释液。然后将平板进行培养，并通过对20个以上细胞的集落进行目视评分来证明生长情况。进行了有限稀释数据分析。对完全加载（约1.8 Ci）的125I原型进行了辐射测量。使用一个校准良好的剂量计来测量完全加载装置的活度。
当该装置加载提供364 - 479 cGy剂量的125I种子时，克隆形成细胞存活的概率为0.033。屏蔽装置外表面的辐射暴露水平在2 - 5 mR/hr范围内，因此符合可接受的正常组织暴露指南。完全加载装置的屏蔽外壳对辐射的衰减为10(-5)。
该装置在髓母细胞瘤细胞被泵入时将其杀死。如果转移风险与克隆形成细胞的数量呈线性相关，那么我们推断该装置将把分流引发转移的风险降低到0.033倍，值得进一步研究。
