Boron neutron capture therapy BNCT behandeling voor Glioblastoom multiforme lijkt een veelbelovende behandeling maar volgens studie aan de VU Amsterdam nog te experimenteel. In Japan wordt BNCT wel succesvol ingezet

18 juli 2011: ik ben kanker-actueel aan het herzien en kwam een aantal studies tegen over Boron Neutron Capture Therapy - BNCT bij hersentumoren. Nu ben ik zelf al eens in Petten op bezoek geweest, toen daar nog BNCT werd gegeven en toen werd BNCT als veelbelovende nieuwe behandeling gezien. Echter in Nederland is daar nooit meer iets mee gedaan. Nu is recent een laboratorium studie gepubliceerd waarin onderzocht is op welke manier BNCT het meest effectief is, in welke dosis, met welke "vloeistof enz.. Voor leken te ingewikkeld vermoed ik maar voor artsen en wetenschappers wel degelijk interessant. Interessant voor leken aan deze studie is dat dit studierapport volledig vrij is in te zien en er een hele lijst aan referenties bij wordt gegeven van studies die de afgelopen 20 jaar zijn gedaan met BNCT. Die referentielijst staat onderaan dit artikel, evenals het abstract van de laboratorium studie.

19 januari 2008 Bron: 1: Pharm World Sci. 2005 Apr;27(2):92-5.

Enkele jaren geleden waren we in Petten op bezoek en daar werd ons verteld dat Boron Neutron Capture Therapy - BNCT een veelbelovende behandeling voor hersentumoren zou zijn. We zagen gedemonstreerd hoe een patiënt een stofje kreeg ingeïnjecteerd, en daarna voor "een gat in de muur" ging liggen". Zover ik me kan herinneren was dat stofje een vorm van lutetium. Dit stofje zou zich alleen in de tumorcellen nestelen en de 'bestraling' uit "het gat in de muur" zou dan de kankercellen kapot maken. In 2006 bleek uit een studie uitgevoerd aan de VU Amsterdam dat er te weinig controle lijkt over de bijwerkingen. De dosis van de bestraling kon niet hoog genoeg zijn om schade aan gezond weefsel te voorkomen. Echter in december 2005 werd een andere Japanse studie gepubliceerd waar een aangepaste vorm van BNCT wel opmerkelijk goede resultaten laat zien. Meer dan 50% van de tumoren bij 8 van de 12 patienten verdween na een eenmalige behandeling. Zie hieronder beide abstracten.

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

Bron: BMC Cancer. 2010; 10: 661.

Published online 2010 December 2. doi: 10.1186/1471-2407-10-661

Peng Wang,^#¹ Haining Zhen,^#¹ Xinbiao Jiang,^#² Wei Zhang,¹ Xin Cheng,³ Geng Guo,¹ Xinggang Mao,¹ and Xiang Zhang¹

¹Department of Neurosurgery of Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R.China

²Northwest Institute of Nuclear Technology, Xi'an, Shaanxi 710024, PR China

³Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China

Corresponding author.

^#Contributed equally.

Peng Wang: wangpeng@fmmu.eud.cn ; Haining Zhen: zhenhn@fmmu.eud.cn ; Xinbiao Jiang: jiangxb67@yahoo.com.cn ; Wei Zhang: nuomi_weiwei@126.com ; Xin Cheng: 15991708409@139.com ; Geng Guo: hainingzhen@yahoo.cn ; Xinggang Mao: jingbowang_fmmu@yahoo.cn ; Xiang Zhang: xzhang@fmmu.edu.cn

Received February 8, 2010; Accepted December 2, 2010.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Other Sections▼

Abstract

Background

Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation.

Methods

The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [⁶⁰Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [⁶⁰Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [⁶⁰Co] γ-rays; Group C included cells treated with 8 Gy of [⁶⁰Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis.

Results

Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [⁶⁰Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with BPA-BNCT were significantly higher than those in Group B and Group C irradiated by [⁶⁰Co] γ-rays (P < 0.01). The clonogenicity of glioma cells was reduced by BPA-BNCT compared with cells treated in the reactor (Group F, G, H, I), and with the control cells (P < 0.01). Upon BPA-BNCT treatment, the Bax level increased in glioma cells, whereas Bcl-2 expression decreased.

Conclusions

Compared with γ-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by BNCT may be related to activation of Bax and downregulation of Bcl-2.

Referentielijst van studies uitgevoerd met BNCT - Boron Neutron Capture Therapy bij hersentumoren

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The BNCT is a promising and possibly curative method of treating GBM, but at present this procedure is far from perfect.

Boron neutron capture therapy for glioblastoma multiforme.van Rij CM, Wilhelm AJ, Sauerwein WA, van Loenen AC.

Department of Pharmacy, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. katja.van.rij@ghz.nl

AIM: Glioblastoma multiforme (GBM) is an incurable disease that can only be managed in a palliative way. The GBM accounts for approximately half of all newly diagnosed primary brain tumors with an incidence of 2-3 cases per 100,000 people each year. Surgery and radiation are the standard options for palliation, and whether there is a place for chemotherapy is still discussed. Boron neutron capture therapy (BNCT) is a promising and possibly curative method of treating GBM. The purpose of this article is to provide an updated review on the current management and future possibilities of treating GBM with BNCT.

METHOD: Use was made of computerized searches and of checking cross-references of articles and book chapters.

RESULTS: The principle of BNCT uses the high ability of 10B to capture thermal neutrons and to disintegrate immediately into a He nucleus (alpha-particle) and a Li nucleus. To reach a sufficient concentration of 10B in the malignant cells compared to the surrounding healthy tissue, 10B-carriers must be highly tumor-selective. At present, the 10B carriers boronophenylalanine (BPA) and sodium borocaptate (BSH) are used in clinical trials to perform BNCT.

CONCLUSION: The BNCT is a promising and possibly curative method of treating GBM, but at present this procedure is far from perfect. Because of the lack of selectivity of the boron carriers, it appears so far that radiation toxicity limits the radiation dose, so that tumor damage is modest. Current investigations and developments are aimed at targeting the boron carriers to the tumor, in order to limit the damage to the healthy, surrounding tissue.

PMID: 15999918 [PubMed - indexed for MEDLINE]

Modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages

J Neurosurg. 2005 Dec;103(6):1000-9
Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages.Miyatake S, Kawabata S, Kajimoto Y, Aoki A, Yokoyama K, Yamada M, Kuroiwa T, Tsuji M, Imahori Y, Kirihata M, Sakurai Y, Masunaga S, Nagata K, Maruhashi A, Ono K. Department of Neurosurgery, Osaka Medical College, Takatsuki City, Japan. neu070@poh.osaka-med.ac.jp

OBJECT: To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds-sodium borocaptate (BSH) and boronophenylalanine (BPA)-with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults.

METHODS: Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent 18F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4-71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3-87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period.

CONCLUSIONS: This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages. PMID: 16381186 [PubMed - indexed for MEDLINE]

hersentumoren, Boron neutron capture therapy, BNCT