Image-guided convection-enhanced delivery of gemcitabine to the brainstem
Image-guided convection-enhanced delivery of gemcitabine to the brainstem
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DOI：
10.3171/jns.2007.106.2.351
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发表时间：
2007-02-01
影响因子：
4.1
通讯作者：
Lonser, Russell R.
中科院分区：
文献类型：
--
作者：
Murad, Gregory J. A.;Walbridge, Stuart;Lonser, Russell R.
目的。为了确定强效抗神经胶质瘤化疗药物吉西他滨是否可以以治疗剂量安全地输送到脑干，同时使用替代磁共振 (MR) 成像示踪剂监测其分布，作者使用对流增强输送将吉西他滨和 Gd-二亚乙基五乙酸 (DTPA) 灌注到灵长类动物脑干。六只灵长类动物接受吉西他滨（0.4 mg/ml；两只动物）、GdDTPA（5 mM；两只动物）或吉西他滨（0.4 mg/ml）和 Gd-DTPA（5 mM；两只动物）的混合脑干灌注，并在 28 天后处死。对这些灵长类动物进行临床观察（六只动物），并通过磁共振成像（五只动物）、定量放射自显影（一只动物）和组织学分析（所有动物）进行观察。 在另一只灵长类动物中，H-3-吉西他滨和 Gd-DTPA 发生混淆，随后立即处死该动物。在灵长类动物中，没有与输注相关的组织毒性的组织学证据。输注液输送过程中获得的磁共振图像表明，输注 Gd-DTPA 的解剖区域与周围未输注的组织清晰可辨。定量放射自显影证实，Gd-DTPA 追踪 3H-吉西他滨的分布，并且非常接近其分布容积（平均分布容积差异 13.5%）。结论。吉西他滨可以以高于临床相关浓度的治疗浓度和体积安全有效地递送至灵长类动物脑干。此外，通过在输注液中添加 Gd-DTPA，MR 成像可用于追踪吉西他滨的分布。这种递送模式应允许吉西他滨直接治疗脑干胶质瘤，同时监测其分布，以确保有效的肿瘤覆盖并最大限度地提高安全性。
Object. To determine if the potent antiglioma chemotherapeutic agent gemcitabine could be delivered to the brainstem safely at therapeutic doses while monitoring its distribution using a surrogate magnetic resonance (MR) imaging tracer, the authors used convection-enhanced delivery to perfuse the primate brainstem with gemcitabine and Gd-diethylenetnamine pentaacetic acid (DTPA).Methods. Six primates underwent convective brainstem perfusion with gemcitabine (0.4 mg/ml; two animals), GdDTPA (5 mM; two animals), or a coinfusion of gemcitabine (0.4 mg/ml) and Gd-DTPA (5 mM; two animals), and were killed 28 days afterward. These primates were observed over time clinically (six animals), and with MR imaging (five animals), quantitative autoradiography (one animal), and histological analysis (all animals).In an additional primate, H-3-gemcitabine and Gd-DTPA were confused and the animal was killed immediately afterward. In the primates there was no histological evidence of infusate-related tissue toxicity. Magnetic resonance images obtained during infusate delivery demonstrated that the anatomical region infused with Gd-DTPA was clearly distinguishable from surrounding noninfused tissue. Quantitative autoradiography confirmed that Gd-DTPA tracked the distribution of 3H-gemcitabine and closely approximated its volume of distribution (mean volume of distribution difference 13.5%).Conclusions. Gemcitabine can be delivered safely and effectively to the primate brainstern at therapeutic concentrations and at volumes that are higher than those considered clinically relevant. Moreover, MR imaging can be used to track the distribution of gemcitabine by adding Gd-DTPA to the infusate. This delivery paradigm should allow for direct therapeutic application of gemcitabine to brainstern gliomas while monitoring its distribution to ensure effective tumor coverage and to maximize safety.