The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

Pavel Bláha, Chiara Feoli, Stefano Agosteo, Marco Calvaruso, Francesco Paolo Cammarata, Roberto Catalano, Mario Ciocca, Giuseppe Antonio Pablo Cirrone, Valeria Conte, Giacomo Cuttone, Angelica Facoetti, Giusi Irma Forte, Lorenzo Giuffrida, Giuseppe Magro, Daniele Margarone, Luigi Minafra, Giada Petringa, Gaia Pucci, Valerio Ricciardi, Enrico RosaGiorgio Russo, Lorenzo Manti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-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 11B 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.

Original languageEnglish
Article number682647
JournalFrontiers in oncology
Volume11
DOIs
Publication statusPublished - 28 Jun 2021

Bibliographical note

Funding Information:
This work was financially supported by 2019-21 INFN grant NEPTUNE (Nuclear process-driven Enhancement of Proton Therapy, UNravEled) and MIUR PRIN2017 PBCT. This work was also supported by European Structural and Investment Fund and the Czech Ministry of Education, Youth and Sports (Project International mobility MSCA-IF IV FZU - CZ.02.2.69/0.0/0.0/20-079/0017754). This research was partially supported by the project “TP01010035 PHysics, Applied Research for Novel TECHnologies” funded by Technology Agency of the Czech Republic.

Publisher Copyright:
© Copyright © 2021 Bláha, Feoli, Agosteo, Calvaruso, Cammarata, Catalano, Ciocca, Cirrone, Conte, Cuttone, Facoetti, Forte, Giuffrida, Magro, Margarone, Minafra, Petringa, Pucci, Ricciardi, Rosa, Russo and Manti.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • alpha-particle
  • BSH
  • cancer cell killing
  • chromosome aberrations
  • proton-boron (B) fusion-enhanced proton therapy (PBFEPT)
  • protontherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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