Capuani Silvia, Gili Tommaso, Bozzali Marco, Russo Salvatore, Porcari Paola, Cametti Cesare, D'Amore Emanuela, Colasanti Marco, Venturini Giorgio, Maraviglia Bruno, Lazzarino Giuseppe, Pastore Francesco S
Physics Department, Sapienza University of Rome, Italy; Enrico Fermi Center, Rome, Italy.
Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):562-7. doi: 10.1016/j.ijrobp.2008.06.1493.
Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on (10)B(n,alpha)(7)Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for (10)B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model.
BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography.
L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples.
This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms.
硼中子俘获疗法（BNCT）是一种基于¹⁰B（n，α）⁷Li反应的放射治疗方式，用于治疗恶性胶质瘤。BNCT疗效的主要限制之一是肿瘤细胞中¹⁰B核素摄取不足。本研究旨在探讨左旋多巴（L-DOPA）作为一种假定的增强剂，在C6胶质瘤模型中增强¹⁰B药物4-二羟基硼苯丙氨酸（BPA）摄取的作用。该研究首先在体外进行，然后扩展到动物模型。
使用射频介电谱评估有无L-DOPA预加载时C6胶质瘤细胞中BPA的积累情况。研究了两种L-DOPA孵育时间（2小时和4小时），并对其对BPA积累的相应影响进行了量化。还将C6胶质瘤细胞植入32只大鼠的脑内，通过磁共振成像监测肿瘤生长。将大鼠分为两个实验组：（1）给予BPA；（2）L-DOPA预处理后给予BPA。处死所有动物，使用高效液相色谱法评估肿瘤组织、正常脑组织和血液样本中BPA的浓度。
仅在孵育4小时后，L-DOPA预加载导致C6胶质瘤细胞中BPA浓度大幅增加。在动物模型中，L-DOPA预处理使肿瘤组织中BPA的积累显著增加，但在正常脑组织和血液样本中未增加。
本研究表明L-DOPA有可能作为增强剂，用于增强适合BNCT的恶性胶质瘤中BPA的积累。从膜转运机制方面讨论了L-DOPA预加载的作用。
