Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam During Helium and Carbon Ion Therapy

Nicholas Howell; Ryan J Middleton; Frederic Sierro; Benjamin H Fraser; Naomi A Wyatt; Andrew Chacon; Keith R Bambery; Elle Livio; Christopher Dobie; Joseph J Bevitt; Justin Davies; Anthony Dosseto; Daniel R Franklin; Ulf Garbe; Susanna Guatelli; Ryoichi Hirayama; Naruhiro Matsufuji; Akram Mohammadi; Karl Mutimer; Louis M Rendina; Anatoly B Rosenfeld; Mitra Safavi-Naeini

doi:10.1016/j.ijrobp.2024.02.052

Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam During Helium and Carbon Ion Therapy

Int J Radiat Oncol Biol Phys. 2024 Mar 11:S0360-3016(24)00368-7. doi: 10.1016/j.ijrobp.2024.02.052. Online ahead of print.

Authors

Nicholas Howell¹, Ryan J Middleton¹, Frederic Sierro¹, Benjamin H Fraser¹, Naomi A Wyatt¹, Andrew Chacon¹, Keith R Bambery¹, Elle Livio¹, Christopher Dobie¹, Joseph J Bevitt¹, Justin Davies¹, Anthony Dosseto², Daniel R Franklin³, Ulf Garbe¹, Susanna Guatelli⁴, Ryoichi Hirayama⁵, Naruhiro Matsufuji⁵, Akram Mohammadi⁵, Karl Mutimer¹, Louis M Rendina⁶, Anatoly B Rosenfeld⁴, Mitra Safavi-Naeini⁷

Affiliations

¹ Australian Nuclear Science and Technology Organisation, Lucas Heights, Australia.
² Wollongong Isotope Geochronology Laboratory, School of Earth, Atmospheric and Life Sciences, University of Wollongong, Wollongong, Australia.
³ School of Electrical and Data Engineering, University of Technology Sydney, Ultimo, Australia.
⁴ Centre for Medical Radiation Physics, University of Wollongong, Wollongong, Australia.
⁵ National Institutes for Quantum Sciences and Technology, Chiba, Japan.
⁶ School of Chemistry, The University of Sydney, Sydney, Australia; The University of Sydney Nano Institute, Sydney, Australia.
⁷ Australian Nuclear Science and Technology Organisation, Lucas Heights, Australia; Centre for Medical Radiation Physics, University of Wollongong, Wollongong, Australia. Electronic address: mitras@ansto.gov.au.

PMID: 38479560
DOI: 10.1016/j.ijrobp.2024.02.052

Abstract

Purpose: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with 2 different targeted neutron capture agents (NCAs).

Methods and materials: Human glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs [¹⁰B]-BPA and [¹⁵⁷Gd]-DOTA-TPP. Cells were positioned within a polymethyl methacrylate phantom either laterally adjacent to or within a 100 × 100 × 60 mm spread out Bragg peak (SOBP). The effect of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in 6 independent experiments. Neutron fluence within the phantom was characterized by quantifying the neutron activation of gold foil.

Results: Cells placed inside the treatment volume reached 10% survival by 2 Gy of carbon or 2 to 3 Gy of helium in the presence of NCAs compared with 5 Gy of carbon and 7 Gy of helium with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of carbon or helium (to the treatment volume), compared with no detectable effect on cells without NCA. The mean thermal neutron fluence at the center of the SOBP was approximately 2.2 × 10⁹ n/cm²/Gy (relative biological effectiveness) for the carbon beam and 5.8 × 10⁹ n/cm²/Gy (relative biological effectiveness) for the helium beam and gradually decreased in all directions.

Conclusions: The addition of NCAs to cancer cells during carbon and helium beam irradiation has a measurable effect on cell survival and growth in vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumors, by targeting this dose to microinfiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumor tissue within the treatment volume, with a reduction in radiation doses to off-target tissue.