{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:53:30Z","timestamp":1781164410999,"version":"3.54.1"},"reference-count":29,"publisher":"IOP Publishing","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biomed. Phys. Eng. Express"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Boron neutron capture therapy (BNCT) dose calculation often relies on fixed relative biological effectiveness (RBE) and compound biological effectiveness (CBE) values, despite their dependence on beam quality and tumor biology. We developed a microdosimetry-driven framework that predicts cell survival and RBE for BNCT by coupling PHITS lineal energy (T-SED) calculations with the microdosimetric kinetic (MK) model. MK parameters (\n                    <jats:italic>\u03b1<\/jats:italic>\n                    <jats:sub>0<\/jats:sub>\n                    ,\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>d<\/jats:italic>\n                    <\/jats:sub>\n                    ,\n                    <jats:italic>y<\/jats:italic>\n                    <jats:sub>0<\/jats:sub>\n                    ) were derived for BNCT relevant cell lines (U87 glioblastoma, NB1RG skin fibroblasts, SAS human squamous carcinoma, and SCC7 murine squamous carcinoma) using low-LET reference datasets curated in the PIDE database and irradiation conditions reproduced in PHITS. The derived parameters successfully reproduced\n                    <jats:italic>in vitro<\/jats:italic>\n                    survival curves for various charged particles across different energies, and when applied to neutron fields representative of BNCT systems (Kyoto University Reactor thermal neutron beam, cyclotron-based epithermal neutron source using a beryllium target, and linear accelerator system using a lithium target), the framework also reproduced measured\n                    <jats:italic>in vitro<\/jats:italic>\n                    data. Predicted RBE at 10% survival (RBE\n                    <jats:sub>10<\/jats:sub>\n                    ) agreed with measurements across cell lines and beam qualities, with only a slight deviation for SCC7 under the CICS spectrum and moderate deviations for SAS due to limited and heterogeneous low-LET datasets in PIDE. This method enables spectrum and cell-line specific estimation of biological effect, supporting replacement of fixed RBE\/CBE with spectrum aware quantities to improve BNCT dose prescription and safety. The framework can also guide neutron-beam design by providing preliminary RBE estimates prior to construction of the moderator and beam shaping assembly. Incorporating intracellular boron microdistribution in future work is expected to refine CBE estimates and enhance biological accuracy in BNCT treatment planning. This framework provides a physics-based alternative to fixed RBE\/CBE values.\n                  <\/jats:p>","DOI":"10.1088\/2057-1976\/ae44a2","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T22:48:23Z","timestamp":1770850103000},"page":"025014","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of a microdosimetry-based method to derive cell survival rates for evaluating the biological effects of BNCT"],"prefix":"10.1088","volume":"12","author":[{"given":"Ryusuke","family":"Yamazaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2702-3344","authenticated-orcid":false,"given":"Naonori","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-6130","authenticated-orcid":true,"given":"Takushi","family":"Takata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-8676","authenticated-orcid":true,"given":"Mai","family":"Nojiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6195-3177","authenticated-orcid":true,"given":"Hiroki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"bpexae44a2bib1","first-page":"1","type":"journal-article","article-title":"Biological effects and therapeutic possibilities of neutrons","volume":"36","author":"Locher","year":"1936","journal-title":"American Journal of Roentgenology, Radium Therapy"},{"key":"bpexae44a2bib2","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.radonc.2020.11.001","type":"journal-article","article-title":"Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): an open-label phase II trial R","volume":"155","author":"Hirose","year":"2021","journal-title":"adiotherapy and Oncology"},{"key":"bpexae44a2bib3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/noajnl\/vdab067","type":"journal-article","article-title":"Accelerator-based BNCT for patients with recurrent glioblastoma: a multicenter phase II study","volume":"3","author":"Kawabata","year":"2021","journal-title":"Neurooncol. Adv."},{"key":"bpexae44a2bib4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-87627-8","type":"journal-article","article-title":"Neutron flux evaluation model provided in the accelerator-based boron neutron capture therapy system employing a solid-state lithium target","volume":"11","author":"Nakamura","year":"2021","journal-title":"Sci Rep."},{"key":"bpexae44a2bib5","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1088\/0031-9155\/38\/12\/002","type":"journal-article","article-title":"A calculation of the energy dependence of the RBE of neutrons","volume":"38","author":"Blue","year":"1993","journal-title":"Phys. Med. Biol."},{"key":"bpexae44a2bib6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13014-021-01968-2","type":"journal-article","article-title":"Evaluation of a treatment planning system developed for clinical boron neutron capture therapy and validation against an independent Monte Carlo dose calculation system","volume":"16","author":"Hu","year":"2021","journal-title":"Radiation Oncology"},{"key":"bpexae44a2bib7","author":"International Commission on Radiation Units and Measurements","year":"1983","type":"other"},{"key":"bpexae44a2bib8","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1080\/00223131.2017.1419890","type":"journal-article","article-title":"Features of particle and heavy ion transport code system (PHITS) version 3.02","volume":"55","author":"Sato","year":"2018","journal-title":"J. Nucl. Sci. Technol."},{"key":"bpexae44a2bib9","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/rpd\/ncl407","type":"journal-article","article-title":"Development of a calculation method for estimating specific energy distribution in complex radiation fields","volume":"122","author":"Sato","year":"2006","journal-title":"Radiat. Prot. Dosimetry"},{"key":"bpexae44a2bib10","first-page":"629","type":"journal-article","volume":"166","author":"Kase","year":"2006","journal-title":"Microdosimetric Measurements and Estimation of Human Cell Survival for Heavy-Ion Beams"},{"key":"bpexae44a2bib11","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41598-017-18871-0","type":"journal-article","article-title":"Microdosimetric modeling of biological effectiveness for boron neutron capture therapy considering intra- and intercellular heterogeneity in 10B distribution","volume":"8","author":"Sato","year":"2018","journal-title":"Sci. Rep."},{"key":"bpexae44a2bib12","type":"dataset","article-title":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung","author":"GSI","year":"2025","unstructured":"GSI 2025 GSI Helmholtzzentrum f\u00fcr Schwerionenforschung PIDE Project \u200b https:\/\/www.gsi.de\/work\/forschung\/biophysik\/forschungsfelder\/radiobiological_modelling\/pide_project (Accessed 12 May 2025)"},{"key":"bpexae44a2bib13","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1093\/jrr\/rrad056","type":"journal-article","article-title":"Experimentally determined relative biological effectiveness of cyclotron-based epithermal neutrons designed for clinical BNCT: in vitro study","volume":"64","author":"Hu","year":"2023","journal-title":"J. Radiat. Res."},{"key":"bpexae44a2bib14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1093\/jrr\/rrad037","type":"journal-article","article-title":"Relative biological effectiveness for epithermal neutron beam contaminated with fast neutrons in the linear accelerator-based boron neutron capture therapy system coupled to a solid-state lithium target","volume":"64","author":"Nakamura","year":"2023","journal-title":"J. Radiat. Res."},{"key":"bpexae44a2bib15","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/jrr\/rry080","type":"journal-article","article-title":"Proposal for determining absolute biological effectiveness of boron neutron capture therapy - the effect of 10B(n,\u03b1)7Li dose can be predicted from the nucleocytoplasmic ratio or the cell size","volume":"60","author":"Ono","year":"2019","journal-title":"J. Radiat. Res."},{"key":"bpexae44a2bib16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1242\/jcs.241869","type":"journal-article","article-title":"Specialization of nuclear membrane in eukaryotes","volume":"133","author":"Hara","year":"2020","journal-title":"J. Cell Sci."},{"key":"bpexae44a2bib17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.apradiso.2020.109148","type":"journal-article","article-title":"Evaluation of PHITS for microdosimetry in BNCT to support radiobiological research","volume":"161","author":"Hu","year":"2020","journal-title":"Appl. Radiat. Isot."},{"key":"bpexae44a2bib18","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1093\/jrr\/rrz101","type":"journal-article","article-title":"Microdosimetric quantities of an accelerator-based neutron source used for boron neutron capture therapy measured using a gas-filled proportional counter","volume":"61","author":"Hu","year":"2020","journal-title":"J. Radiat. Res."},{"key":"bpexae44a2bib19","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/jrr\/rry099","type":"journal-article","article-title":"The radiobiological effects of He, C and Ne ions as a function of LET on various glioblastoma cell lines","volume":"60","author":"Chew","year":"2019","journal-title":"J. Radiat. Res."},{"key":"bpexae44a2bib20","doi-asserted-by":"publisher","DOI":"10.1063\/1.3699063","type":"journal-article","article-title":"Biological effectiveness on live cells of laser driven protons at dose rates exceeding 109 Gy\/s","volume":"2","author":"Doria","year":"2012","journal-title":"AIP Adv."},{"key":"bpexae44a2bib21","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1667\/RR3360","type":"journal-article","article-title":"LET and ion species dependence for cell killing in normal human skin fibroblasts","volume":"163","author":"Tsuruoka","year":"2005","journal-title":"Radiat. Res."},{"key":"bpexae44a2bib22","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1080\/09553000110066095","type":"journal-article","article-title":"p53-Dependent thermal enhancement of cellular sensitivity in human squamous cell carcinomas in relation to LET","volume":"77","author":"Takahashi","year":"2001","journal-title":"Int. J. Radiat. Biol."},{"key":"bpexae44a2bib23","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1269\/jrr.08052","type":"journal-article","article-title":"Effectiveness of monoenergetic and spread-out bragg peak carbon-ions for inactivation of various normal and tumour human cell lines","volume":"49","author":"Belli","year":"2008","journal-title":"J. Radiat. Res."},{"key":"bpexae44a2bib24","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1016\/j.nimb.2009.03.095","type":"journal-article","article-title":"Characteristics comparison between a cyclotron-based neutron source and KUR-HWNIF for boron neutron capture therapy","volume":"267","author":"Tanaka","year":"2009","journal-title":"Nucl. Instrum. Methods Phys. Res. B"},{"key":"bpexae44a2bib25","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/S0168-9002(00)00465-4","type":"journal-article","article-title":"Characteristics of the KUR heavy water neutron irradiation facility as a neutron irradiation field with variable energy spectra","volume":"453","author":"Sakurai","year":"2000","journal-title":"Nucl. Instrum. Methods Phys. Res. A"},{"key":"bpexae44a2bib26","first-page":"199","type":"book","article-title":"chapter Eighteen - Proton linear accelerator and lithium target system","author":"Kaneta","year":"2023"},{"key":"bpexae44a2bib27","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.ijrobp.2007.10.050","type":"journal-article","article-title":"Radiobiologic parameters and local effect model predictions for head-and-neck squamous cell carcinomas exposed to high linear energy transfer ions","volume":"71","author":"Beuve","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"bpexae44a2bib28","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/0360-3016(95)02180-9","type":"journal-article","article-title":"Radiobiological evidence suggesting heterogeneous microdistribution of boron compounds in tumors: its relation to quiescent cell population and tumor cure in neutron capture therapy","volume":"34","author":"Ono","year":"1996","journal-title":"International Journal of Radiation Oncology*Biology*Physics"},{"key":"bpexae44a2bib29","doi-asserted-by":"publisher","first-page":"6980","DOI":"10.1021\/jm300749q","type":"journal-article","article-title":"Biological evaluation of dodecaborate-containing l -amino acids for boron neutron capture therapy","volume":"55","author":"Hattori","year":"2012","journal-title":"J. Med. Chem."}],"container-title":["Biomedical Physics &amp; Engineering Express"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:53:53Z","timestamp":1771520033000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/2057-1976\/ae44a2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,19]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1088\/2057-1976\/ae44a2","relation":{},"ISSN":["2057-1976"],"issn-type":[{"value":"2057-1976","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"assertion":[{"value":"Development of a microdosimetry-based method to derive cell survival rates for evaluating the biological effects of BNCT","name":"article_title","label":"Article Title"},{"value":"Biomedical Physics & Engineering Express","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2026 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2025-09-25","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-02-11","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-02-19","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}