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首页> 外文期刊>Neurosurgery >Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning.
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Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning.

机译：对流性增强对恶性神经胶质瘤患者的脑内输注液分布：靶解剖和导管定位的描述性作用。

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OBJECTIVE: Convection-enhanced delivery (CED) holds tremendous potential for drug delivery to the brain. However, little is known about the volume of distribution achieved within human brain tissue or how target anatomy and catheter positioning influence drug distribution. The primary objective of this study was to quantitatively describe the distribution of a high molecular weight agent by CED relative to target anatomy and catheter position in patients with malignant gliomas. METHODS: Seven adult patients with recurrent malignant gliomas underwent intracerebral infusion of the tumor-targeted cytotoxin, cintredekin besudotox, concurrently with 123I-labeled human serum albumin. High-resolution single-photon emission computed tomographic images were obtained at 24 and 48 hours and were coregistered with magnetic resonance imaging scans. The distribution of 123I-labeled human serum albumin relative to target anatomy and catheter position was analyzed. RESULTS: Intracerebral CED infusions were well-tolerated and some resulted in a broad distribution of 123I-labeled human serum albumin, but target anatomy and catheter positioning had a significant influence on infusate distribution even within non-contrast-enhancing areas of brain. Intratumoral infusions were anisotropic and resulted in limited coverage of the enhancing tumor area and adjacent peritumoral regions. CONCLUSIONS: CED has the potential to deliver high molecular weight agents into tumor-infiltrated brain parenchyma with volumes of distribution that are clinically relevant. Target tissue anatomy and catheter position are critical parameters in optimizing drug delivery.
机译：目的：对流增强输送（CED）具有将药物输送到大脑的巨大潜力。但是，关于人脑组织内的分布量或靶标解剖结构和导管位置如何影响药物分布的知识知之甚少。这项研究的主要目的是定量描述CED在恶性神经胶质瘤患者中相对于目标解剖结构和导管位置的高分子量药物分布。方法：7例成人恶性神经胶质瘤复发患者接受脑内输注靶向肿瘤的细胞毒素，cintredekin besudotox和123I标记的人血清白蛋白。高分辨率的单光子发射计算机断层扫描图像是在24和48小时获得的，并与磁共振成像扫描共同记录。分析了123I标记的人血清白蛋白相对于靶标解剖结构和导管位置的分布。结果：脑内CED输注耐受性良好，有的导致123I标记人血清白蛋白的广泛分布，但即使在脑部非造影剂增强区域内，靶标解剖结构和导管位置也对输注液分布有重大影响。肿瘤内输注是各向异性的，导致增强的肿瘤区域和相邻的肿瘤周围区域的覆盖范围有限。结论：CED具有将高分子量药物输送到肿瘤浸润的脑实质中的潜力，其分布量与临床相关。目标组织解剖结构和导管位置是优化药物输送的关键参数。

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