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Biology of Boron Neutron Capture Therapy (BNCT) 2021

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 12804

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Special Issue Editors

Prof. Dr. Wolfgang Sauerwein

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Guest Editor

1. Radiation Oncology, University Hospital Essen, University Duisburg, Strahlenklinik, Hufeland Street 55, 45122 Essen, Germany
2. Neutron Therapy Research Center, Okayama University, Okayama 700-8530, Japan
3. German Society for Boron Neutron Capture Therapy, 45122 Essen, Germany
Interests: radiation oncology; hadron therapy; boron neutron capture therapy (BNCT); neutrons; high-LET radiation; radiation biology; eye tumors; ophthalmic oncology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Mitsuko Masutani

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Guest Editor

1. Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
2. Visiting Scientist, Central Radioisotope Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Interests: radiation oncology; biology in anti-cancer treatment; polyADP-ribosylation; anti-tumor therapeutic; mouse; boron neutron capture therapy
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Prof. Dr. John Hopewell

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Guest Editor

Radiobiological Research, University of Oxford, Oxford OX1 2JD, UK
Interests: clinically oriented radiation biology
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Special Issue Information

Dear Colleagues,

The appearance of hospital-based epithermal neutron sources has made boron neutron capture therapy (BNCT) a dedicated focus of innovative developments in radiation oncology. All future clinical applications have to be based on carefully performed pre-clinical investigations. At this very moment, it seems appropriate and important to collect results of recent preclinical and early clinical research and publish them together with intelligible and clear reviews of the most challenging aspects of BNCT.

This Special Issue of Cells is for contributions on all cytobiological aspects related to BNCT. You are invited to submit your contributions in the form of original research articles, reviews, or shorter perspective articles.

Relevant observations made at the cellular level could come from the following areas:

Radiation biology for BNCT;
Cell-based studies;
Preclinical animal studies;
Drug development for BNCT;
Impact of BNCT on the proteomic profile and omics approaches;
Boron imaging;
Mechanisms of action of BNCT;
Abscopal effect of BNCT;
Early clinical trials;
Biomarkers for therapeutic optimization.

Prof. Wolfgang Sauerwein
Prof. Mitsuko Masutani
Prof. John Hopewell
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Related Special Issues

Biology of Boron Neutron Capture Therapy (BNCT) in Cells (10 articles)
BNCT Drug Development and Preclinical Testing in Cells (5 articles)
Cell Biology for Boron Neutron Capture Therapy (BNCT) in Cells

Published Papers (4 papers)

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Research

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11 pages, 2338 KiB

Open AccessArticle

A Novel Boron Lipid to Modify Liposomal Surfaces for Boron Neutron Capture Therapy

by Makoto Shirakawa, Alexander Zaboronok, Kei Nakai, Yuhki Sato, Sho Kayaki, Tomonori Sakai, Takao Tsurubuchi, Fumiyo Yoshida, Takashi Nishiyama, Minoru Suzuki, Hisao Tomida and Akira Matsumura

Cells 2021, 10(12), 3421; https://doi.org/10.3390/cells10123421 - 05 Dec 2021

Cited by 8 | Viewed by 2481

Abstract

Boron neutron capture therapy (BNCT) is a cancer treatment with clinically demonstrated efficacy using boronophenylalanine (BPA) and sodium mercaptododecaborate (BSH). However, tumor tissue selectivity of BSH and retention of BPA in tumor cells is a constant problem. To ensure boron accumulation and retention in tumor tissues, we designed a novel polyethylene glycol (PEG)-based boron-containing lipid (PBL) and examined the potency of delivery of boron using novel PBL-containing liposomes, facilitated by the enhanced permeability and retention (EPR) effect. PBL was synthesized by the reaction of distearoylphosphoethanolamine and BSH linked by PEG with Michael addition while liposomes modified using PBL were prepared from the mixed lipid at a constant molar ratio. In this manner, novel boron liposomes featuring BSH in the liposomal surfaces, instead of being encapsulated in the inner aqueous phase or incorporated in the lipid bilayer membrane, were prepared. These PBL liposomes also carry additional payload capacity for more boron compounds (or anticancer agents) in their inner aqueous phase. The findings demonstrated that PBL liposomes are promising candidates to effect suitable boron accumulation for BNCT. Full article

(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT) 2021)

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Review

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11 pages, 280 KiB

Open AccessReview

Response of Normal Tissues to Boron Neutron Capture Therapy (BNCT) with ¹⁰B-Borocaptate Sodium (BSH) and ¹⁰B-Paraboronophenylalanine (BPA)

by Hiroshi Fukuda

Cells 2021, 10(11), 2883; https://doi.org/10.3390/cells10112883 - 26 Oct 2021

Cited by 18 | Viewed by 3073

Abstract

Boron neutron capture therapy (BNCT) is a cancer-selective radiotherapy that utilizes the cancer targeting ¹⁰B-compound. Cancer cells that take up the compound are substantially damaged by the high liner energy transfer (LET) particles emitted mainly from the ¹⁰B(n, α⁷Li reaction. BNCT can minimize the dose to normal tissues, but it must be performed within the tolerable range of normal tissues. Therefore, it is important to evaluate the response of normal tissues to BNCT. Since BNCT yields a mixture of high and low LET radiations that make it difficult to understand the radiobiological basis of BNCT, it is important to evaluate the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for assessing the responses of normal tissues to BNCT. BSH and BPA are the only ¹⁰B-compounds that can be used for clinical BNCT. Their biological behavior and cancer targeting mechanisms are different; therefore, they affect the CBE values differently. In this review, we present the RBE and CBE values of BPA or BSH for normal tissue damage by BNCT irradiation. The skin, brain (spinal cord), mucosa, lung, and liver are included as normal tissues. The CBE values of BPA and BSH for tumor control are also discussed. Full article

(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT) 2021)

13 pages, 710 KiB

Open AccessReview

Boron Neutron Capture Therapy (BNCT) for Cutaneous Malignant Melanoma Using ¹⁰B-p-Boronophenylalanine (BPA) with Special Reference to the Radiobiological Basis and Clinical Results

by Hiroshi Fukuda

Cells 2021, 10(11), 2881; https://doi.org/10.3390/cells10112881 - 26 Oct 2021

Cited by 23 | Viewed by 3198

Abstract

BNCT is a radiotherapeutic method for cancer treatment that uses tumor-targeting ¹⁰B-compounds. BNCT for cutaneous melanoma using BPA, a phenylalanine derivative, was first initiated by Mishima et al. in 1987. This article reviews the radiobiological basis of melanoma control and damage to normal tissues as well as the results of clinical studies. Experimental studies showed that the compound biological effectiveness (CBE) values of the ¹⁰B (n, α)⁷Li reaction for melanoma control ranged from 2.5 to 3.3. The CBE values of the ¹⁰B (n, α)⁷Li reaction for skin damage ranged from 2.4 to 3.7 with moist desquamation as the endpoint. The required single radiation dose for controlling human melanoma was estimated to be 25 Gy-Eq or more by analyzing the 50% tumor control dose data of conventional fractionated radiotherapy. From the literature, the maximum permissible dose to human skin by single irradiation was estimated to be 18 Gy-Eq. With respect to the pharmacokinetics of BPA in patients with melanoma treated with 85–350 mg/kg BPA, the melanoma-to-blood ratio ranged from 2.1–3.8 and the skin-to-blood ratio was 1.31 ± 0.22. Good local tumor control and long-term survival of the patients were achieved in two clinical trials of BNCT conducted in Japan. Full article

(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT) 2021)

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10 pages, 1733 KiB

Open AccessReview

Development of an Imaging Technique for Boron Neutron Capture Therapy

by Nobuyoshi Fukumitsu and Yoshitaka Matsumoto

Cells 2021, 10(8), 2135; https://doi.org/10.3390/cells10082135 - 19 Aug 2021

Cited by 5 | Viewed by 2847

Abstract

The development of 4-¹⁰B-borono-2-¹⁸F-fluoro-L-phenylalanine (¹⁸FBPA) for use in positron emission tomography (PET) has contributed to the progress of boron neutron capture therapy (BNCT). ¹⁸FBPA has shown similar pharmacokinetics and distribution to 4-¹⁰B-borono-L-phenylalanine (BPA) under various conditions in many animal studies. ¹⁸FBPA PET is useful for treatment indication. A higher ¹⁸FBPA accumulation ratio of the tumor to the surrounding normal tissue (T/N ratio) indicates that a superior treatment effect is expected. In clinical settings, a T/N ratio of higher than 2.5 or 3 is often used for patient selection. Moreover, ¹⁸FBPA PET is useful for predicting the ¹⁰B concentration delivered to the tumor and surrounding normal tissues, enabling high-precision treatment planning. Precise dose prediction using ¹⁸FBPA PET data has greatly improved the treatment accuracy of BNCT. However, the methodology used for the data analysis of ¹⁸FBPA PET findings varies; thus, data should be evaluated using a consistent methodology so as to be more reliable. In addition to PET applications, the development of ¹⁸FBPA as a contrast agent for magnetic resonance imaging that combines gadolinium and ¹⁰B is also in progress. Full article

(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT) 2021)

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