PMID- 29348437 OWN - NLM STAT- MEDLINE DCOM- 20181123 LR - 20240313 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Jan 18 TI - First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness. PG - 1141 LID - 10.1038/s41598-018-19258-5 [doi] LID - 1141 AB - Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) (12)C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper (12)C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + (11)B --> 3alpha reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses (10)B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and (12)C-ion therapy is thus demonstrated. FAU - Cirrone, G A P AU - Cirrone GAP AUID- ORCID: 0000-0001-5733-9281 AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. pablo.cirrone@lns.infn.it. FAU - Manti, L AU - Manti L AUID- ORCID: 0000-0003-0168-5040 AD - Physics Department, University of Naples Federico II, Naples, Italy. AD - INFN Naples Section, Complesso Universitario di Monte S. Angelo, Via Cintia, Naples, Italy. FAU - Margarone, D AU - Margarone D AD - Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, Na Slovance 2, Prague, 18221, Czech Republic. FAU - Petringa, G AU - Petringa G AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. AD - Physics Department, University of Catania, via S. Sofia, 64, Catania, Italy. FAU - Giuffrida, L AU - Giuffrida L AD - Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, Na Slovance 2, Prague, 18221, Czech Republic. FAU - Minopoli, A AU - Minopoli A AD - Physics Department, University of Naples Federico II, Naples, Italy. FAU - Picciotto, A AU - Picciotto A AD - Fondazione Bruno Kessler, Micro-Nano Facility, Via Sommarive 18, 38123, Povo-Trento, Italy. FAU - Russo, G AU - Russo G AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. AD - Institute of Molecular Bioimaging and Physiology - National Research Council - (IBFM-CNR), Cefalu, (PA), Italy. FAU - Cammarata, F AU - Cammarata F AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. AD - Institute of Molecular Bioimaging and Physiology - National Research Council - (IBFM-CNR), Cefalu, (PA), Italy. FAU - Pisciotta, P AU - Pisciotta P AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. AD - Physics Department, University of Catania, via S. Sofia, 64, Catania, Italy. FAU - Perozziello, F M AU - Perozziello FM AD - Physics Department, University of Naples Federico II, Naples, Italy. AD - INFN Naples Section, Complesso Universitario di Monte S. Angelo, Via Cintia, Naples, Italy. FAU - Romano, F AU - Romano F AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. AD - National Physical Laboratory, Acoustic and Ionizing Radiation Division, Teddington, TW11 0LW, Middlesex, United Kingdom. FAU - Marchese, V AU - Marchese V AUID- ORCID: 0000-0001-7183-5687 AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. FAU - Milluzzo, G AU - Milluzzo G AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. AD - Physics Department, University of Catania, via S. Sofia, 64, Catania, Italy. FAU - Scuderi, V AU - Scuderi V AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. AD - Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, Na Slovance 2, Prague, 18221, Czech Republic. FAU - Cuttone, G AU - Cuttone G AD - Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali dei Sud, via S. Sofia, 62, Catania, Italy. FAU - Korn, G AU - Korn G AD - Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, Na Slovance 2, Prague, 18221, Czech Republic. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180118 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Borohydrides) RN - 0 (Carbon Isotopes) RN - 0 (DNA, Neoplasm) RN - 0 (Fluorescent Dyes) RN - 0 (Sulfhydryl Compounds) RN - 12294-22-3 (mercaptoundecahydrododecaborate) RN - N9E3X5056Q (Boron) SB - IM MH - Alpha Particles/therapeutic use MH - Animals MH - Borohydrides/chemistry MH - Boron/chemistry/*therapeutic use MH - Boron Neutron Capture Therapy/instrumentation/*methods MH - Carbon Isotopes/chemistry MH - Cell Death/radiation effects MH - Cell Line, Tumor MH - Chromosome Aberrations/radiation effects MH - Combined Modality Therapy/instrumentation/*methods MH - Cyclotrons MH - DNA Damage MH - DNA, Neoplasm/genetics/metabolism/radiation effects MH - Dose-Response Relationship, Radiation MH - Fluorescent Dyes/chemistry MH - Humans MH - Karyotyping MH - Linear Energy Transfer MH - Male MH - *Neutrons MH - Prostatic Neoplasms/pathology/*radiotherapy MH - *Proton Therapy/instrumentation/*methods MH - Relative Biological Effectiveness MH - Sulfhydryl Compounds/chemistry PMC - PMC5773549 COIS- The main author, on behalf of whole collaboration, declare that Dr GAP Cirrone, L Giuffrida, D Margarone, A Picciotto submitted an European patent on the use of 11B for cancer therapy and diagnostic. The other authors have not competing financial interests related to this work. EDAT- 2018/01/20 06:00 MHDA- 2018/11/24 06:00 PMCR- 2018/01/18 CRDT- 2018/01/20 06:00 PHST- 2017/01/26 00:00 [received] PHST- 2017/12/27 00:00 [accepted] PHST- 2018/01/20 06:00 [entrez] PHST- 2018/01/20 06:00 [pubmed] PHST- 2018/11/24 06:00 [medline] PHST- 2018/01/18 00:00 [pmc-release] AID - 10.1038/s41598-018-19258-5 [pii] AID - 19258 [pii] AID - 10.1038/s41598-018-19258-5 [doi] PST - epublish SO - Sci Rep. 2018 Jan 18;8(1):1141. doi: 10.1038/s41598-018-19258-5.