Convection enhanced delivery of carboranylporphyrins for neutron capture therapy of brain tumors.
Convection enhanced delivery of carboranylporphyrins for neutron capture therapy of brain tumors.
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DOI：
10.1007/s11060-010-0376-5
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发表时间：
2011-06
影响因子：
3.9
通讯作者：
Vicente MG
中科院分区：
文献类型：
--
作者：
Kawabata S;Yang W;Barth RF;Wu G;Huo T;Binns PJ;Riley KJ;Ongayi O;Gottumukkala V;Vicente MG
硼中子俘获治疗（BNCT）是基于非放射性10 B被低能热中子辐照产生α粒子（10 B [n，α] 7 Li）时发生的核俘获和裂变反应。碳硼烷卟啉是一类含有多个碳硼烷簇的取代卟啉。本文对其中的三种卟啉化合物进行了评价：5，10，15，20-四-（4-巢式碳硼烷基苯基）四苯并卟啉（H_2TBP）、5，10，15，20-四-（4-巢式碳硼烷基苯基）卟啉（H_2TCP）和5，15-二-[3，5-（巢式碳硼烷基甲基）苯基]卟啉（H_2DCP）。这项研究的目的是双重的。首先，为了确定脑内（i.c.）通过短期（30分钟）对流增强递送（CED）或通过渗透泵持续递送超过24小时的方式向携带F98胶质瘤的大鼠施用。第二，确定H2 TCP和H2 TBP作为硼递送剂用于荷F98胶质瘤大鼠的BNCT的功效。i.c.渗透泵输送量高（36-88 µg/g），24 h时仍保持高水平（62-103 µg/g），相应的正常脑浓度低（0.8-5.2 µg/g），血液和肝脏浓度均无法检测到。基于这些数据，在CED或渗透泵输送后24小时，在马萨诸塞州理工学院（MIT）研究反应堆（MITRR）用H2 TCP和H2 TBP开始治疗研究。未处理和辐照对照大鼠的平均存活时间（MST）分别为23±3和27±3天，而接受H2 TCP或H2 TBP，随后接受BNCT的动物的MST分别为35±4天和44±10天，这优于静脉内给予硼苯丙氨酸后获得的MST（37±3天）。然而，由于碳硼烷卟啉的肿瘤硼浓度是静脉注射BPA（~25 µg/g）的3- 5倍，我们预期MST会更高。BNCT治疗大鼠脑组织病理学检查显示，有大量的卟啉负载的巨噬细胞，以及卟啉的细胞外积累，表明看似高的肿瘤硼浓度并不代表真正的肿瘤细胞摄取。我们的数据是第一次表明，碳硼烷卟啉是有效的实验性脑肿瘤的BNCT传递剂。基于这些结果，我们现在正在评估碳硼烷卟啉的过程中，它可以在给药后增强细胞摄取并提高治疗效果。
Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive 10B is irradiated with low energy thermal neutrons to produce α-particles (10B[n,α]7Li). Carboranylporphyrins are a class of substituted porphyrins containing multiple carborane clusters. Three of these have been evaluated in the present study: 5,10,15,20-tetra-(4-nido-carboranyphenyl)tetrabenzoporphyrin (H2TBP), 5,10,15,20-tetra-(4-nido-carboranylphenyl)porphyrin (H2TCP) and 5,15-di-[3,5-(nido-carboranylmethyl)phenyl]-porphyrin (H2DCP). The goals of this study were two-fold. First, to determine the biodistribution of H2TBP, H2TCP and H2DCP following intracerebral (i.c.) administration by means of short term (30 min) convection enhanced delivery (CED) or sustained delivery over 24 h by osmotic pumps to F98 glioma bearing rats. Second, to determine the efficacy of H2TCP and H2TBP as boron delivery agents for BNCT in F98 glioma bearing rats. Tumor boron concentrations immediately after i.c. osmotic pump delivery were high (36–88 µg/g) and they remained so at 24 h (62–103 µg/g) The corresponding normal brain concentrations were low (0.8–5.2 µg/g) and the blood and liver concentrations were all undetectable. Based on these data, therapy studies were initiated at the Massachusetts Institute of Technology (MIT) Research Reactor (MITRR) with H2TCP and H2TBP 24 h after CED or osmotic pump delivery. Mean survival times (MST) of untreated and irradiated control rats were 23±3 and 27±3 d, respectively, while animals that received H2TCP or H2TBP, followed by BNCT, had a MST of 35±4 d and 44±10 d, respectively, which were better than those obtained following i.v. administration of boronophenylalanine (37±3 d). However, since the tumor boron concentrations of the carboranylporphyrins were 3–5X > i.v. BPA (~25 µg/g), we had expected that the MSTs would have been greater. Histopathologic examination of brains of BNCT treated rats revealed that there were large numbers of porphyrin-laden macrophages, as well as extracellular accumulations of porphyrins indicating that the seemingly high tumor boron concentrations did not represent the true tumor cellular uptake. Our data are the first to show that carboranyl porphyrins are effective delivery agents for BNCT of an experimental brain tumor. Based on these results, we now are in the process of evaluating carboranylporphyrins that could have enhanced cellular uptake following administration and improved therapeutic efficacy.
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影响因子：
4.1
作者：
CEBERG, CP;BRUN, A;SALFORD, LG
通讯作者：
SALFORD, LG
DOI：
10.1016/j.jphotobiol.2007.09.012
发表时间：
2007-12-14
影响因子：
5.4
作者：
Fabris, Clara;Vicente, M. Graca H.;Soncin, Marina
通讯作者：
Soncin, Marina
DOI：
10.1016/s0360-3016(00)00421-1
发表时间：
2000-04-01
影响因子：
7
作者：
Barth, RF;Yang, WL;Goodman, JH
通讯作者：
Goodman, JH
影响因子：
1.5
作者：
Bobadova-Parvanova, P;Oku, Y;Vicente, MGH
通讯作者：
Vicente, MGH
影响因子：
3.5
作者：
Gottumukkala, V;Ongayi, O;Vicente, MGH
通讯作者：
Vicente, MGH