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Biology of Boron Neutron Capture Therapy (BNCT)
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Biology of Boron Neutron Capture Therapy (BNCT)

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 44188

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
Dr. Amanda Elena Schwint

E-Mail Website
Guest Editor
1. Head Radiation Pathology Division, Department of Radiobiology, National Atomic Energy Commission (CNEA), General Paz 1499, San Martín, Provincia de Buenos Aires B1650KNA, Argentina
2. Principal Investigator of the National Research Council of Argentina (CONICET), Buenos Aires, Argentina
Interests: boron neutron capture therapy (BNCT) radiobiology; particle therapy; translational in vivo BNCT studies; clinical veterinary BNCT studies; interdisciplinary national and international collaborations
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Mitsuko Masutani

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. John Hopewell

E-Mail Website
Guest Editor
Radiobiological Research, University of Oxford, Oxford OX1 2JD, UK
Interests: clinically oriented radiation biology
Special Issues, Collections and Topics in MDPI journals

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.

In this Special Issue of Cells, we invite your contributions, in the form of original research articles, reviews, or shorter perspective articles, on all cellular aspects related to the theme of BNCT.

Relevant topics include, but are not limited to, the following:

  • 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.

Dr. Wolfgang Sauerwein
Dr. Amanda Schwint
Prof. Mitsuko Masutani
Prof. John Hopewell
Guest Editors

Manuscript Submission Information

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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.

Keywords

  • boron neutron capture therapy (BNCT)
  • radiation biology
  • radiation oncology
  • clinical trials
  • drug development
  • imaging

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Published Papers (10 papers)

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23 pages, 4623 KiB  
Article
Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy
by Seth W. Streitmatter, Robert D. Stewart, Gregory Moffitt and Tatjana Jevremovic
Cells 2020, 9(10), 2302; https://doi.org/10.3390/cells9102302 - 15 Oct 2020
Cited by 14 | Viewed by 3287
Abstract
Accurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of [...] Read more.
Accurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of models to better assess the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) of several neutron sources as applied to BNCT using boronophenylalanine (BPA) and a potential monoclonal antibody (mAb) that targets HER-2-positive cells with Trastuzumab. The multiscale model is tested against published in vitro and in vivo measurements of cell survival with and without boron. The combined dosimetric and radiobiological model includes an analytical formulation that accounts for the type of neutron source, the tissue- or cancer-specific dose–response characteristics, and the microdistribution of boron. Tests of the model against results from published experiments with and without boron show good agreement between modeled and experimentally determined cell survival for neutrons alone and in combination with boron. The system of models developed in this work is potentially useful as an aid for the optimization and individualization of BNCT for HER-2-positive cancers, as well as other cancers, that can be targeted with mAb or a conventional BPA compound. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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20 pages, 6228 KiB  
Article
In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy
by Atsushi Fujimura, Seiji Yasui, Kazuyo Igawa, Ai Ueda, Kaori Watanabe, Tadashi Hanafusa, Yasuaki Ichikawa, Sachiko Yoshihashi, Kazuki Tsuchida, Atsunori Kamiya and Shuichi Furuya
Cells 2020, 9(10), 2149; https://doi.org/10.3390/cells9102149 - 23 Sep 2020
Cited by 21 | Viewed by 4373
Abstract
Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer [...] Read more.
Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44High cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44High cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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14 pages, 2809 KiB  
Article
Thermal Neutron Relative Biological Effectiveness Factors for Boron Neutron Capture Therapy from In Vitro Irradiations
by María Pedrosa-Rivera, Javier Praena, Ignacio Porras, Manuel P. Sabariego, Ulli Köster, Michael Haertlein, V. Trevor Forsyth, José C. Ramírez, Clara Jover, Daniel Jimena, Juan L. Osorio, Patricia Álvarez, Carmen Ruiz-Ruiz and María J. Ruiz-Magaña
Cells 2020, 9(10), 2144; https://doi.org/10.3390/cells9102144 - 23 Sep 2020
Cited by 2 | Viewed by 3434
Abstract
The experimental determination of the relative biological effectiveness of thermal neutron factors is fundamental in Boron Neutron Capture Therapy. The present values have been obtained while using mixed beams that consist of both neutrons and photons of various energies. A common weighting factor [...] Read more.
The experimental determination of the relative biological effectiveness of thermal neutron factors is fundamental in Boron Neutron Capture Therapy. The present values have been obtained while using mixed beams that consist of both neutrons and photons of various energies. A common weighting factor has been used for both thermal and fast neutron doses, although such an approach has been questioned. At the nuclear reactor of the Institut Laue-Langevin a pure low-energy neutron beam has been used to determine thermal neutron relative biological effectiveness factors. Different cancer cell lines, which correspond to glioblastoma, melanoma, and head and neck squamous cell carcinoma, and non-tumor cell lines (lung fibroblast and embryonic kidney), have been irradiated while using an experimental arrangement designed to minimize neutron-induced secondary gamma radiation. Additionally, the cells were irradiated with photons at a medical linear accelerator, providing reference data for comparison with that from neutron irradiation. The survival and proliferation were studied after irradiation, yielding the Relative Biological Effectiveness that corresponds to the damage of thermal neutrons for the different tissue types. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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14 pages, 2327 KiB  
Article
Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications
by Ghadir Kalot, Amélie Godard, Benoît Busser, Jacques Pliquett, Mans Broekgaarden, Vincent Motto-Ros, Karl David Wegner, Ute Resch-Genger, Ulli Köster, Franck Denat, Jean-Luc Coll, Ewen Bodio, Christine Goze and Lucie Sancey
Cells 2020, 9(9), 1953; https://doi.org/10.3390/cells9091953 - 25 Aug 2020
Cited by 31 | Viewed by 6502
Abstract
Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on the nuclear capture of slow neutrons by stable 10B atoms followed by charged particle emission that inducing extensive damage on a very localized level (<10 μm). To be efficient, a sufficient [...] Read more.
Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on the nuclear capture of slow neutrons by stable 10B atoms followed by charged particle emission that inducing extensive damage on a very localized level (<10 μm). To be efficient, a sufficient amount of 10B should accumulate in the tumor area while being almost cleared from the normal surroundings. A water-soluble aza-boron-dipyrromethene dyes (BODIPY) fluorophore was reported to strongly accumulate in the tumor area with high and BNCT compatible Tumor/Healthy Tissue ratios. The clinically used 10B-BSH (sodium borocaptate) was coupled to the water-soluble aza-BODIPY platform for enhanced 10B-BSH tumor vectorization. We demonstrated a strong uptake of the compound in tumor cells and determined its biodistribution in mice-bearing tumors. A model of chorioallantoic membrane-bearing glioblastoma xenograft was developed to evidence the BNCT potential of such compound, by subjecting it to slow neutrons. We demonstrated the tumor accumulation of the compound in real-time using optical imaging and ex vivo using elemental imaging based on laser-induced breakdown spectroscopy. The tumor growth was significantly reduced as compared to BNCT with 10B-BSH. Altogether, the fluorescent aza-BODIPY/10B-BSH compound is able to vectorize and image the 10B-BSH in the tumor area, increasing its theranostic potential for efficient approach of BNCT. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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9 pages, 2344 KiB  
Article
Water-Soluble closo-Docecaborate-Containing Pteroyl Derivatives Targeting Folate Receptor-Positive Tumors for Boron Neutron Capture Therapy
by Fumiko Nakagawa, Hidehisa Kawashima, Taiki Morita and Hiroyuki Nakamura
Cells 2020, 9(7), 1615; https://doi.org/10.3390/cells9071615 - 3 Jul 2020
Cited by 19 | Viewed by 3228
Abstract
Water-soluble pteroyl-closo-dodecaborate conjugates (PBCs 1–4), were developed as folate receptor (FRα) targeting boron carriers for boron neutron capture therapy (BNCT). PBCs 1–4 had adequately low cytotoxicity with IC50 values in the range of 1~3 mM toward selected human cancer cells, [...] Read more.
Water-soluble pteroyl-closo-dodecaborate conjugates (PBCs 1–4), were developed as folate receptor (FRα) targeting boron carriers for boron neutron capture therapy (BNCT). PBCs 1–4 had adequately low cytotoxicity with IC50 values in the range of 1~3 mM toward selected human cancer cells, low enough to use as BNCT boron agents. PBCs 1–3 showed significant cell uptake by FRα positive cells, especially U87MG glioblastoma cells, although the accumulation of PBC 4 was low compared with PBCs 1–3 and L-4-boronophenylalanine (L-BPA). The cellular uptake of PBC 1 and PBC 3 by HeLa cells was arrested by increasing the concentration of folate in the medium, indicating that the major uptake mechanisms of PBC 1–3 are primarily through FRα receptor-mediated endocytosis. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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13 pages, 1678 KiB  
Article
Synthesis and Evaluation of Dodecaboranethiol Containing Kojic Acid (KA-BSH) as a Novel Agent for Boron Neutron Capture Therapy
by Koji Takeuchi, Yoshihide Hattori, Shinji Kawabata, Gen Futamura, Ryo Hiramatsu, Masahiko Wanibuchi, Hiroki Tanaka, Shin-ichiro Masunaga, Koji Ono, Shin-Ichi Miyatake and Mitsunori Kirihata
Cells 2020, 9(6), 1551; https://doi.org/10.3390/cells9061551 - 25 Jun 2020
Cited by 18 | Viewed by 3711
Abstract
Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 (10B) to produce high-linear energy transfer (LET) alpha particles and recoiling 7Li nuclei (10B [n, alpha] 7Li) in [...] Read more.
Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 (10B) to produce high-linear energy transfer (LET) alpha particles and recoiling 7Li nuclei (10B [n, alpha] 7Li) in tumor cells. Therefore, it is important to achieve the selective delivery of large amounts of 10B to tumor cells, with only small amounts of 10B to normal tissues. To develop practical materials utilizing 10B carriers, we designed and synthesized novel dodecaboranethiol (BSH)-containing kojic acid (KA-BSH). In the present study, we evaluated the effects of this novel 10B carrier on cytotoxicity, 10B concentrations in F98 rat glioma cells, and micro-distribution of KA-BSH in vitro. Furthermore, biodistribution studies were performed in a rat brain tumor model. The tumor boron concentrations showed the highest concentrations at 1 h after the termination of administration. Based on these results, neutron irradiation was evaluated at the Kyoto University Research Reactor Institute (KURRI) with KA-BSH. Median survival times (MSTs) of untreated and irradiated control rats were 29.5 and 30.5 days, respectively, while animals that received KA-BSH, followed by neutron irradiation, had an MST of 36.0 days (p = 0.0027, 0.0053). Based on these findings, further studies are warranted in using KA-BSH as a new B compound for malignant glioma. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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18 pages, 3011 KiB  
Article
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy
by Marcos Couto, Catalina Alamón, María Fernanda García, Mariángeles Kovacs, Emiliano Trias, Susana Nievas, Emiliano Pozzi, Paula Curotto, Silvia Thorp, María Alejandra Dagrosa, Francesc Teixidor, Clara Viñas and Hugo Cerecetto
Cells 2020, 9(6), 1408; https://doi.org/10.3390/cells9061408 - 5 Jun 2020
Cited by 29 | Viewed by 4005
Abstract
One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop [...] Read more.
One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro–BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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20 pages, 9019 KiB  
Article
Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT
by Takao Tsurubuchi, Makoto Shirakawa, Wataru Kurosawa, Kayo Matsumoto, Risa Ubagai, Hiroshi Umishio, Yasuyo Suga, Junko Yamazaki, Akihiro Arakawa, Yutaka Maruyama, Takuya Seki, Yusuke Shibui, Fumiyo Yoshida, Alexander Zaboronok, Minoru Suzuki, Yoshinori Sakurai, Hiroki Tanaka, Kei Nakai, Eiichi Ishikawa and Akira Matsumura
Cells 2020, 9(5), 1277; https://doi.org/10.3390/cells9051277 - 21 May 2020
Cited by 40 | Viewed by 5217
Abstract
Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as 10B delivery agents. However, continuous drug administration at high concentrations is needed [...] Read more.
Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as 10B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient 10B concentration within tumors. To address the issue of 10B accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing α-d-mannopyranoside. We evaluated the uptake, intracellular distribution, and retention of MMT1242 in cultured cells and analyzed biodistribution, tumor-to-normal tissue ratio and toxicity in vivo. Fluorescence imaging using nitrobenzoxadiazole (NBD)-labeled MMT1242 and inductively coupled mass spectrometry (ICP-MS) were performed. The effectiveness of BNCT using MMT1242 was assessed in animal irradiation studies at the Kyoto University Research Reactor. MMT1242 showed a high uptake and broad intracellular distribution in vitro, longer tumor retention compared to BSH and BPA, and adequate tumor-to-normal tissue accumulation ratio and low toxicity in vivo. A neutron irradiation study with MMT1242 in a subcutaneous murine tumor model revealed a significant tumor inhibiting effect if injected 24 h before irradiation. We therefore report that 10B-MMT1242 is a candidate for further clinical BNCT studies. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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16 pages, 2596 KiB  
Article
A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy
by Yusuke Matsuya, Hisanori Fukunaga, Motoko Omura and Hiroyuki Date
Cells 2020, 9(5), 1117; https://doi.org/10.3390/cells9051117 - 30 Apr 2020
Cited by 27 | Viewed by 4125
Abstract
Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both [...] Read more.
Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of 10B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the 10B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric–kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to 60Co γ-rays, thermal neutrons, and BNCT with 10B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to 60Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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11 pages, 2497 KiB  
Perspective
Quantification of Boron Compound Concentration for BNCT Using Positron Emission Tomography
by Marcin Balcerzyk, Manuel De-Miguel, Carlos Guerrero and Begoña Fernandez
Cells 2020, 9(9), 2084; https://doi.org/10.3390/cells9092084 - 12 Sep 2020
Cited by 9 | Viewed by 3685
Abstract
Background: Boron neutron capture therapy requires a 2 mM 10B concentration in the tumor. The well-known BNCT patient treatment method using boronophenylalanine (BPA) as a boron-carrying agent utilizes [18F]fluoroBPA ([18F]FBPA) as an agent to qualify for treatment. [...] Read more.
Background: Boron neutron capture therapy requires a 2 mM 10B concentration in the tumor. The well-known BNCT patient treatment method using boronophenylalanine (BPA) as a boron-carrying agent utilizes [18F]fluoroBPA ([18F]FBPA) as an agent to qualify for treatment. Precisely, [18F]FBPA must have at least a 3:1 tumor to background tissue ratio to qualify the patient for BNCT treatment. Normal, hyperplasia, and cancer thyroids capture iodine and several other large ions, including BF4−, through a sodium-iodine symporter (NIS) expressed on the cell surface in normal conditions. In cancer, NIS is also expressed within the thyroid cell and is not functional. Methods: To visualize the thyroids and NIS, we have used a [18F]NaBF4 positron emission tomography (PET) tracer. It was injected into the tail veins of rats. The [18F]NaBF4 PET tracer was produced from NaBF4 by the isotopic exchange of natural 19F with radioactive 18F. Rats were subject to hyperplasia and tumor-inducing treatment. The NIS in thyroids was visualized by immunofluorescence staining. The boron concentration was calculated from Standard Uptake Values (SUV) in the PET/CT images and from the production data. Results: 41 MBq, 0.64 pmol of [18F]NaBF4 PET tracer that contained 0.351 mM, 53 nmol of NaBF4 was injected into the tail vein. After 17 min, the peak activity in the thyroid reached 2.3 MBq/mL (9 SUVmax). The natB concentration in the thyroid with hyperplasia reached 381 nM. Conclusions: Such an incorporation would require an additional 110 mg/kg dose of [10B]NaBF4 to reach the necessary 2 mM 10B concentration in the tumor. For future BNCT treatments of thyroid cancer, contrary to the 131I used now, there is no post-treatment radioactive decay, the patient can be immediately discharged from hospital, and there is no six-month moratorium for pregnancy. This method can be used for BNCT treatment compounds of the type R-BFn, where 1 <= n <= 3, labeled with 18F relatively easily, as in our example. A patient may undergo injection of a mixture of nonradioactive R-BFn to reach the necessary 10B concentration for BNCT treatment in the tumor together, with [18F]R-BFn for boron mapping. Full article
(This article belongs to the Special Issue Biology of Boron Neutron Capture Therapy (BNCT))
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