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, Shin‐Ichi; Kawabata, Shinji; Kajimoto, Yoshinaga; Aoki, Atsushi; Yokoyama, Kunio; Yamada, Makoto; Kuroiwa, Toshihiko; Tsuji, Motomu; Imahori, Yoshio; Kirihata, Mitsunori; Sakurai, Yoshinori; Masunaga, Shin‐ichiro; Nagata, Kenji; Maruhashi, Akira; Ono, Koji

doi:10.3171/jns.2005.103.6.1000

Cited by 127 publications

(82 citation statements)

References 17 publications

(18 reference statements)

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“…The data that we have obtained with the mAbs L8A4 and cetuximab define two characteristics of EGFR targeting bioconjugates that make them promising boron delivery agents for use in combination with either BPA alone or with BPA and BSH as is currently being evaluated in Japan (54). The data shown in Tables 3 and 4 indicate that CED of BD-L8A4 was more effective than i.v.…”

Section: Discussionmentioning

confidence: 58%

Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4

Yang¹,

Barth²,

Wu³

et al. 2006

Clinical Cancer Research

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Purpose: The purpose of the present study was to evaluate a boronated EGFRvIII-specific monoclonal antibody, L8A4, for boron neutron capture therapy (BNCT) of the receptor-positive rat glioma, F98 npEGFRvIII . Experimental Design: A heavily boronated polyamido amine (PAMAM) dendrimer (BD) was chemically linked to L8A4 by two heterobifunctional reagents, N-succinimidyl 3-(2-pyridyldithio)propionate and N-(k-maleimidoundecanoic acid)hydrazide. For in vivo studies, F98 wild-type receptor-negative or EGFRvIII human gene-transfected receptor-positive F98 npEGFRvIII glioma cells were implanted i.c. into the brains of Fischer rats. Biodistribution studies were initiated 14 days later. Animals received [125 I]BD-L8A4 by either convection enhanced delivery (CED) or direct i.t. injection and were euthanized 6, 12, 24, or 48 hours later. Results: At 6 hours, equivalent amounts of the bioconjugate were detected in receptor-positive and receptor-negative tumors, but by 24 hours the amounts retained by receptor-positive gliomas were 60.1% following CED and 43.7% following i.t. injection compared with 14.6% ID/g by receptor-negative tumors. Boron concentrations in normal brain, blood, liver, kidneys, and spleen all were at nondetectable levels (<0.5 Ag/g) at the corresponding times. Based on these favorable biodistribution data, BNCT studies were initiated at the Massachusetts Institute of Technology Research Reactor-II. Rats received BD-L8A4 (f40 Ag

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Section: Discussionmentioning

confidence: 58%

Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4

Yang¹,

Barth²,

Wu³

et al. 2006

Clinical Cancer Research

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“…Miyatake et al (5) reported that all of their patients who suffered from brain tumors exhibited alopecia, whereas no acute brain swelling or disturbance of consciousness occurred following BNCT. Moreover, Kato et al (7) reported few side effects, such as transient mucositis and alopecia, following BNCT therapy for head and neck tumors.…”

Section: Discussionmentioning

confidence: 99%

“…However, certain patients suffer from alopecia and/or mucositis after undergoing BNCT (3,5). For planning, as well as predicting the outcome and adverse effects of this therapy, boron concentrations should be evaluated in surrounding normal structures as well as in the tumor itself, for which fluorine-18-labeled boronophenylalanine ( 18 F-BPA) PET was utilized.…”

Section: Introductionmentioning

confidence: 99%

Fluorine-18-labeled boronophenylalanine positron emission tomography for oral cancers: Qualitative and quantitative analyses of malignant tumors and normal structures in oral and maxillofacial regions

et al. 2011

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Abstract. The present study aimed to demonstrate the features of fluorine-18-labeled boronophenylalanine positron emission tomography ( 18 F-BPA-PET) to reveal oral cancer, as well as normal structures in the oral and maxillofacial regions. We analyzed 18 F-BPA-PET findings from 8 patients with histologically confirmed recurrent and/or advanced oral cancer scheduled for boron neutron capture therapy. The capacity of 18 F-BPA-PET to delineate tumor and normal structures was assessed qualitatively and quantitatively. Tumors were easily identified as high uptake areas in all cases. Although the eyes, which were depicted as a low uptake area, and tongue musculature were readily identified, major vessels were not noted in any of the cases. Areas corresponding to the surface of the dorsum tongue to middle pharynx were expressed as high uptake areas in all of the cases. Quantitatively, tumors were expressed as the highest uptake area in 6 of the 8 cases, while the dorsum tongue had the highest uptake area in the remaining 2 cases.18 F-BPA-PET is useful in demonstrating the presence of a tumor. Thus, it is crucial to note the presence of a high uptake area corresponding to the dorsum area of the tongue when diagnosing a tumor using this technique. IntroductionFluorodeoxyglucose (FDG) positron emission tomography (PET) has recently become widely used for detecting malignant tumors of the oral cavity, particularly for the diagnosis of metastatic deposits (1). In addition, another type of PET method, methionine-basis PET, has been shown to be useful for diagnosing malignancies (2).Boron neutron capture therapy (BNCT) was recently performed in order to regulate non-resectable advanced and/or recurrent oral cancers, and its clinical utility was previously reported (3,4). However, certain patients suffer from alopecia and/or mucositis after undergoing BNCT (3,5). For planning, as well as predicting the outcome and adverse effects of this therapy, boron concentrations should be evaluated in surrounding normal structures as well as in the tumor itself, for which fluorine-18-labeled boronophenylalanine ( 18 F-BPA) PET was utilized. To the best of our knowledge, features of normal tissues and tumors in 18 F-BPA-PET images have yet to be adequately assessed. The present study therefore aimed to qualitatively and quantitatively elucidate the features of normal structures in the oral and maxillofacial regions, as well as associated tumors revealed by 18 F-BPA-PET imaging. Materials and methodsThe study evaluated 18 F-BPA-PET images obtained in examinations of 8 patients with histologically confirmed recurrent and/or advanced oral cancer, or metastatic lymphadenopathy who were scheduled for BNCT (Table I). Seven of the patients were treated with a combination of surgery, chemotherapy and radiotherapy, while 1 patient was treated with thermotherapy. All PET examinations were performed using an ECAT ACCEL (Siemens Japan Co., Tokyo, Japan) with 18 F-labeled BPA (37-55.5 MBq/10 kg of body weight) injected 45 min prior to obtaining the im...

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“…In Japan, Miyatake et al (15) and Kawabata et al (26,27) performed studies in which either BPA alone or in combination with BSH was administered as BNCT. They reported that patients treated with surgery and BNCT using 100 mg/kg BSH and 700 mg/kg BPA infused over 6 hours, followed by 20-30 Gy of fractionated X-rays had an MST of 23.5 months.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it facilitates achieving the appropriate head position and -angle with respect to the neutron beam port during irradiation. In 2004, boronophenylalanine (BPA), a new boron compound that is actively taken up by tumor cells (15), was introduced for the treatment of GBM with BNCT. The introduction of the epithermal neutron beam, the clinical use of BPA, and the dose planning system of JCDS made the clinical use of nonoperative BNCT (NO-BNCT) combined with BSH and BPA a reality.…”

Section: Introductionmentioning

confidence: 99%

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

et al. 2014

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: The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months ; the 2-, 3-, and 5-year survival rates were 31.8% %, 22.7% %, and 9.1% %, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

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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

Abstract: This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.

Cited by 127 publications

References 17 publications

Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4

Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4

Fluorine-18-labeled boronophenylalanine positron emission tomography for oral cancers: Qualitative and quantitative analyses of malignant tumors and normal structures in oral and maxillofacial regions

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

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