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左旋多巴预负荷显著增加了C6胶质瘤模型中硼代苯丙氨酸的摄取。

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading.

作者信息

Capuani S, Gili T, Bozzali M, Russo S, Porcari P, Cametti C, Muolo M, D'Amore E, Maraviglia B, Lazzarino G, Pastore F S

机构信息

CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome, Italy.

出版信息

Appl Radiat Isot. 2009 Jul;67(7-8 Suppl):S34-6. doi: 10.1016/j.apradiso.2009.03.017. Epub 2009 Mar 26.

Abstract

One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

摘要

硼中子俘获疗法(BNCT)有效性的主要限制之一是肿瘤细胞内(10)B核素摄取不足。本研究旨在探讨左旋多巴(L-DOPA)作为硼苯丙氨酸(BPA)摄取增强剂在C6胶质瘤模型中的应用。研究首先在体外进行,然后扩展到动物模型体内。使用无线电波介电谱(RDS)评估有无L-DOPA预加载情况下C6胶质瘤细胞中BPA的积累。将C6胶质瘤细胞植入25只大鼠的脑内,随机分为两个实验组:(1)颈动脉内注入BPA;(2)在注入BPA前24小时用L-DOPA预处理后颈动脉内注入BPA。处死所有动物,使用高效液相色谱法(HPLC)评估肿瘤组织、正常脑组织和血液样本中BPA的浓度。L-DOPA预加载在体外C6胶质瘤细胞或动物模型肿瘤体内均导致BPA浓度大幅增加。此外,两组动物的正常脑组织和血液样本中未发现显著差异。本研究表明L-DOPA有可能作为BPA在适合BNCT的恶性胶质瘤中积累的增强剂。

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