PMID- 34262867 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210716 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives. PG - 682647 LID - 10.3389/fonc.2021.682647 [doi] LID - 682647 AB - Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and (11)B atoms, i.e. p+(11)B--> 3alpha (p-B), which is supposed to produce highly-DNA damaging alpha-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as (11)B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index. CI - Copyright (c) 2021 Blaha, Feoli, Agosteo, Calvaruso, Cammarata, Catalano, Ciocca, Cirrone, Conte, Cuttone, Facoetti, Forte, Giuffrida, Magro, Margarone, Minafra, Petringa, Pucci, Ricciardi, Rosa, Russo and Manti. FAU - Blaha, Pavel AU - Blaha P AD - Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Napoli, Naples, Italy. FAU - Feoli, Chiara AU - Feoli C AD - Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Napoli, Naples, Italy. FAU - Agosteo, Stefano AU - Agosteo S AD - Energy Department, Politecnico di Milano, and INFN, Sezione di Milano, Milan, Italy. FAU - Calvaruso, Marco AU - Calvaruso M AD - Istituto di Bioimmagini e Fisiologia Molecolare-Consiglio Nazionale delle Ricerche (IBFM-CNR), Cefalu, Italy. AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. FAU - Cammarata, Francesco Paolo AU - Cammarata FP AD - Istituto di Bioimmagini e Fisiologia Molecolare-Consiglio Nazionale delle Ricerche (IBFM-CNR), Cefalu, Italy. AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. FAU - Catalano, Roberto AU - Catalano R AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. FAU - Ciocca, Mario AU - Ciocca M AD - Medical Physics Unit & Research Department, Centro Nazionale di Adroterapia Oncologica (CNAO) & INFN, Sezione di Pavia, Pavia, Italy. FAU - Cirrone, Giuseppe Antonio Pablo AU - Cirrone GAP AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. FAU - Conte, Valeria AU - Conte V AD - Laboratori Nazionali di Legnaro (LNL), INFN, Legnaro, Italy. FAU - Cuttone, Giacomo AU - Cuttone G AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. FAU - Facoetti, Angelica AU - Facoetti A AD - Medical Physics Unit & Research Department, Centro Nazionale di Adroterapia Oncologica (CNAO) & INFN, Sezione di Pavia, Pavia, Italy. FAU - Forte, Giusi Irma AU - Forte GI AD - Istituto di Bioimmagini e Fisiologia Molecolare-Consiglio Nazionale delle Ricerche (IBFM-CNR), Cefalu, Italy. AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. FAU - Giuffrida, Lorenzo AU - Giuffrida L AD - Extreme Light Infrastructure (ELI)-Beamlines Center, Institute of Physics (FZU), Czech Academy of Sciences, Prague, Czechia. FAU - Magro, Giuseppe AU - Magro G AD - Medical Physics Unit & Research Department, Centro Nazionale di Adroterapia Oncologica (CNAO) & INFN, Sezione di Pavia, Pavia, Italy. FAU - Margarone, Daniele AU - Margarone D AD - Extreme Light Infrastructure (ELI)-Beamlines Center, Institute of Physics (FZU), Czech Academy of Sciences, Prague, Czechia. FAU - Minafra, Luigi AU - Minafra L AD - Istituto di Bioimmagini e Fisiologia Molecolare-Consiglio Nazionale delle Ricerche (IBFM-CNR), Cefalu, Italy. AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. FAU - Petringa, Giada AU - Petringa G AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. AD - Extreme Light Infrastructure (ELI)-Beamlines Center, Institute of Physics (FZU), Czech Academy of Sciences, Prague, Czechia. FAU - Pucci, Gaia AU - Pucci G AD - Istituto di Bioimmagini e Fisiologia Molecolare-Consiglio Nazionale delle Ricerche (IBFM-CNR), Cefalu, Italy. AD - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), Universita di Palermo, Palermo, Italy. FAU - Ricciardi, Valerio AU - Ricciardi V AD - Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Napoli, Naples, Italy. AD - Department of Mathematics & Physics, Universita L. Vanvitelli, Caserta, Italy. FAU - Rosa, Enrico AU - Rosa E AD - Radiation Biophysics Laboratory, Department of Physics "E. Pancini", Universita di Napoli Federico II, Naples, Italy. FAU - Russo, Giorgio AU - Russo G AD - Istituto di Bioimmagini e Fisiologia Molecolare-Consiglio Nazionale delle Ricerche (IBFM-CNR), Cefalu, Italy. AD - Laboratori Nazionali del Sud (LNS), INFN, Catania, Italy. AD - The Sicilian Center of Nuclear Physics and the Structure of Matter (CSFNSM), Catania, Italy. FAU - Manti, Lorenzo AU - Manti L AD - Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Napoli, Naples, Italy. AD - Radiation Biophysics Laboratory, Department of Physics "E. Pancini", Universita di Napoli Federico II, Naples, Italy. LA - eng PT - Journal Article DEP - 20210628 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8274279 OTO - NOTNLM OT - BSH OT - alpha-particle OT - cancer cell killing OT - chromosome aberrations OT - proton-boron (B) fusion-enhanced proton therapy (PBFEPT) OT - protontherapy COIS- Author LG, DM and GAPC declare a potential conflict of interest being patent holder of the following invention: "DEVICE AND METHOD FOR IMAGING AND ENHANCED PROTONTHERAPY TREATMENT USING NUCLEAR REACTIONS. Application no.: EP16178280.0 - 1109/3266470. The remaining authors declare that the work described in this paper was conducted in the absence of any specific relationship that could be construed as a potential conflict of interest. EDAT- 2021/07/16 06:00 MHDA- 2021/07/16 06:01 PMCR- 2021/01/01 CRDT- 2021/07/15 06:23 PHST- 2021/03/18 00:00 [received] PHST- 2021/05/17 00:00 [accepted] PHST- 2021/07/15 06:23 [entrez] PHST- 2021/07/16 06:00 [pubmed] PHST- 2021/07/16 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.682647 [doi] PST - epublish SO - Front Oncol. 2021 Jun 28;11:682647. doi: 10.3389/fonc.2021.682647. eCollection 2021.