Effectiveness of BNCT for recurrent head and neck malignancies

Kato, Ikunoshin; Ono, Koji; Sakurai, Yoshinori; Ohmae, Masatoshi; Maruhashi, Akira; Imahori, Yoshio; Kirihata, Mitsunori; Nakazawa, Mitsuhiro; Yura, Yoshiaki

doi:10.1016/j.apradiso.2004.05.059

Cited by 268 publications

(167 citation statements)

References 5 publications

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“…It has already been used in patients with various types of brain malignances, including glioblastomas (7)(8)(9)(10)(11)(12), anaplastic meningiomas (13), cerebral melanoma metastases (14), or tumors recurrences in inoperable anatomic locations (15,16). In this context, a few Phase I (7,8,10,11) and Phase II studies (8,10) have consistently demonstrated no severe effects of BNCT-related toxicity, and some preliminary evidence of therapeutic effectiveness (7,9,12) has been presented.…”

Section: Introductionmentioning

confidence: 99%

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

Capuani

Gili

Bozzali

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10 B(n,a) 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. Methods and Materials: 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. Results: 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. Conclusions: 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. Ó

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Section: Introductionmentioning

confidence: 99%

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

Capuani

Gili

Bozzali

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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“…10 (3). It was used in clinical trials to treat glioblastoma and melanoma (10 -12) and in combination with BSH to treat squamous cell carcinoma of head and neck (13,14).…”

Section: Animals and Tumorsmentioning

confidence: 99%

Laser postionization secondary neutral mass spectrometry in tissue: a powerful tool for elemental and molecular imaging in the development of targeted drugs

Wittig¹,

Arlinghaus

Kriegeskotte

et al. 2008

Molecular Cancer Therapeutics

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The exact intracellular localization and distribution of molecules and elements becomes increasingly important for the development of targeted therapies and contrast agents. We show that laser postionization secondary neutral mass spectrometry (laser-SNMS) is well suited to localize particular elements and small molecules with subcellular spatial resolution applying the technique exemplary to Boron Neutron Capture Therapy (BNCT). We showed in a murine sarcoma that the drugs used for clinical BNCT, namely L-para-boronophenylalanine (700 mg/kg body weight i.p.) and sodium mercaptoundecahydrocloso-dodecaborate (200 mg/kg body weight i.p.), transport the therapeutic agent 10 B into the cytoplasm and into the nucleus itself, the most sensitive area of the cell. Sodium mercaptoundecahydro-closo-dodecaborate distributes 10 B homogeneously and L-para-boronophenylalanine heterogeneously. When combining laser-SNMS with prompt ;-ray analysis as a screening technique, strategies for BNCT can be elaborated to develop new drugs or to improve the use of existing drugs on scientifically based evidence. The study shows the power of laser-SNMS in the early stages of drug development, also outside BNCT.

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“…The low toxicity of BSH and the fact that 1 molecule transports as many as 12 10 B-atoms, stimulated work to test the compound in peripheral tumors. 16 In our study design, its suitability was evaluated based on the 10 Bconcentration ratios of metastasis/liver and metastasis/blood, with the result that BSH is not suitable to treat liver metastases from colorectal cancer. In most tumor lesions, BSH did not accumulate.…”

Section: Sodium Mercaptoundecahydro-closo-dodecaboratementioning

confidence: 99%

“…12 It was used in clinical trials to treat glioblastoma and melanoma [13][14][15] and combined with BSH in squamous cell carcinoma of head and neck. 16,17 Since 1986, a research program at the University of Pavia (Italy) has been underway to investigate the possibility to cure diffuse hepatic metastases by explanting the liver and irradiating the organ with BNCT followed by an autotransplantation. [18][19][20][21] Within this program, 2 patients have been treated achieving tumor remission.…”

mentioning

confidence: 99%

Uptake of two ¹⁰B‐compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001)

Wittig

Malagó

Collette

et al. 2007

Intl Journal of Cancer

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Disseminated metastases of colorectal cancer in liver are incurable. The trial EORTC 11001 investigates whether autotransplantation after extracorporeal irradiation of the liver by boron neutron capture therapy (BNCT) might become a curative treatment option because of selective uptake of the compounds sodium mercaptoundecahydro-closo-dodecaborate (BSH) or L-para-boronophenylalanine (BPA). BSH (50 mg/kg bw) or BPA (100 mg/kg bw) were infused into patients who subsequently underwent resection of hepatic metastases. Blood and tissue samples were analyzed for the 10 B-concentration with prompt gamma ray spectroscopy (PGRS). Three patients received BSH and 3 received BPA. Adverse effects from the boron carriers did not occur. For BSH, the highest 10 B-concentration was observed in liver (31.5 6 2.7 lg/ g) followed by blood (24.8 6 4.7 lg/g) and tumor (23.2 6 2.1 lg/g) with a mean 10 B-concentration ratio metastasis/liver of 0.72 6 0.07. For BPA, the highest 10 B-concentration was measured in metastases (12.1 6 2.2 lg/g) followed by liver (8.5 6 0.5 lg/g) and blood (5.8 6 0.8 lg/g). As BPA is transported actively into cells, viable, metabolically active cells accumulate exclusively this compound. Consequently, a model is proposed to adjust the values measured by PGRS for the proportion of viable cells to express the relevant 10 B-concentration in the tumor cells, revealing a 10 Bconcentration ratio metastasis/liver of 6.8 6 1.7. In conclusion, BSH is not suitable as 10 B-carrier in liver metastases as the 10 Bconcentration in liver was higher compared to metastasis. BPA accumulates in hepatic metastases to an extent that allows for extracorporeal irradiation of the liver with BNCT. ' 2007 Wiley-Liss, Inc.

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Effectiveness of BNCT for recurrent head and neck malignancies

Cited by 268 publications

References 5 publications

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

Laser postionization secondary neutral mass spectrometry in tissue: a powerful tool for elemental and molecular imaging in the development of targeted drugs

Uptake of two ¹⁰B‐compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001)

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Effectiveness of BNCT for recurrent head and neck malignancies

Cited by 268 publications

References 5 publications

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

Laser postionization secondary neutral mass spectrometry in tissue: a powerful tool for elemental and molecular imaging in the development of targeted drugs

Uptake of two 10B‐compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001)

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Uptake of two ¹⁰B‐compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001)