Sampson John H, Akabani Gamal, Friedman Allan H, Bigner Darell, Kunwar Sandeep, Berger Mitchel S, Bankiewicz Krystof S
Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, North Carolina 27710, USA.
Neurosurg Focus. 2006 Apr 15;20(4):E14. doi: 10.3171/foc.2006.20.4.9.
Convection-enhanced delivery (CED) is a novel technique used to deliver agents to the brain parenchyma for treatment of neoplastic, infectious, and degenerative conditions. The purpose of this study was to determine if CED would provide a larger volume of distribution (Vd) of a radiolabeled monoclonal antibody (mAb) than a bolus injection.
Patients harboring a recurrent glioblastoma multiforme that reacted with the antitenascin mAb 81C6 during immunohistochemical analysis were randomized to receive an intratumoral injection of the human-murine chimeric mAb Ch81C6, which had been labeled with the 123I tracer. The mAb was administered by either a bolus injection or CED via a stereotactically placed catheter; between 48 and 72 hours later the mAb was again administered using the other technique. Injections of escalating doses of a 131I-labeled therapeutic mAb were then delivered using the technique shown to produce the largest Vd by single-photon emission computerized tomography.
Convection-enhanced delivery has enormous potential for administering drugs to sites within the central nervous system. For the relatively small volumes injected in this study, however, CED did not provide a significant increase in the Vd when compared with the bolus injection. Nevertheless, a clear cross-over effect was seen, which was probably related to the temporal proximity of the two infusions.
对流增强递送(CED)是一种用于将药物递送至脑实质以治疗肿瘤、感染和退行性疾病的新技术。本研究的目的是确定与单次推注相比,CED 是否能使放射性标记单克隆抗体(mAb)的分布容积(Vd)更大。
在免疫组织化学分析中与抗腱生蛋白 mAb 81C6 发生反应的复发性多形性胶质母细胞瘤患者被随机分组,接受瘤内注射用 123I 示踪剂标记的人鼠嵌合 mAb Ch81C6。mAb 通过单次推注或经立体定向放置的导管进行 CED 给药;在 48 至 72 小时后,使用另一种技术再次给药 mAb。然后使用通过单光子发射计算机断层扫描显示能产生最大 Vd 的技术,给予递增剂量的 131I 标记治疗性 mAb 注射。
对流增强递送在向中枢神经系统内的部位给药方面具有巨大潜力。然而,对于本研究中注射的相对较小体积,与单次推注相比,CED 并未使 Vd 显著增加。尽管如此,观察到明显的交叉效应,这可能与两次输注在时间上的接近有关。