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Enhancement of proton therapy effectiveness experimentally demonstrated for the first time: Proton Boron Capture Therapy (PBCT)

The use of proton-boron nuclear fusion to enhance proton therapy effectiveness in the cancer cell killing rate has been demonstrated experimentally as a result of a scientific collaboration among researchers coming from Laboratori Nazionali del Sud (LNS-INFN) in Catania, ELI-Beamlines (ELI-IoP-ASCR) in Prague, Department of Physics of University of Naples Federico II (DoP-UoN), and Fondazione Bruno Kessler (FBK) in Trento. The experimental research, carried out at LNS, is a result of two years of intensive experimental activity based on trials with various cell lines.
Image: The CATANA tumor treatment room at LNS-INFN, Catania, Italy (courtesy of G. Agnello)

The experimental technique named PBCT (Proton Boron Capture Therapy) uses molecules containing 11B nuclei which can potentially be administered onto a deep-seated tumor and then bombarded with a proton beam typically used in hadrontherapy. As a consequence of the interaction of one proton with one 11B nucleus, three alpha-particles with low energy (around 4 MeV) are generated and ultimately stopped inside the tumor, thus releasing their entire energy in a single cancer cell. The macroscopic effect is enhanced biological damage compared to that caused only by the incoming protons.

“This result is of high scientific and clinical interest since it may allow widening and improving current hadrontherapy procedures, and can also have a relevant societal impact”, highlights Pablo Cirrone, Medical Physicists at LNS, “the scientific collaboration with ELI-Beamlines started several years ago with the ELIMED project”.

“Proton-boron fusion is a field of research we have been investigating experimentally for many years in Prague by using “laser accelerators”, explains Daniele Margarone, Senior Researcher at ELI, “our close scientific collaboration with INFN, UoN and FBK allowed us to explore the clinical field using a conventional accelerator at LNS in Catania: such synergy was the key to reaching such an interesting result”.

The innovative PBCT enhances the radiobiological effectiveness of proton therapy while at the same time keeping its unique ballistic properties, thus paving the way towards treatment of radioresistant tumors, such as glioma or pancreas tumors. “This study is an elegant example of potentially clinically relevant results that can be achieved by interdisciplinary applied research, combining expertise from various fields that marry physics, biology and, hopefully in the near future, medicine” explains Lorenzo Manti, professor at UoN.

“Societal applications of high power lasers are being investigated at ELI”, highlights Georg Korn, Scientific Director of ELI, “medical applications have a high priority on our research activity agenda, as demonstrated by the ELIMED joint project with INFN and the recent national intersectoral research grant application together with the Prague proton therapy center”.

For more details see:

1, G.A.P. Cirrone, L. Manti, D. Margarone et al., “First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness” Scientific Reports 8 (2018) 1141.

https://www.nature.com/articles/s41598-018-19258-5

2, L. Giuffrida, D. Margarone, G. Korn, G.A.P. Cirrone, A. Picciotto, “Device and method for imaging and enhanced proton-therapy treatment using nuclear reactions”, EP3266470 (A1), EPO patent application (2016).

https://worldwide.espacenet.com/publicationDetails/biblio?CC=EP&NR=3266470&KC=&locale=en_EP&FT=E

3, L. Giuffrida, D. Margarone, G.A.P. Cirrone, A. Picciotto, G. Cuttone, G. Korn, “Prompt gamma ray diagnostics and enhanced hadron-therapy using neutron-free nuclear reactions”, AIP Advances 6 (2016) 105204.

http://aip.scitation.org/doi/abs/10.1063/1.4965254

4, G. Petringa et al., “Prompt gamma-ray emission for future imaging applications in proton-boron fusion therapy”, Journal of Instrumentation 12 (2017) C03059.

http://iopscience.iop.org/article/10.1088/1748-0221/12/03/C03059

 

 

 Schematic representation of “conventional” radiotherapy by low-LET proton beams (left) and the rationale of boron-enhanced protontherapy (right). Whereas in conventional radiotherapy the incident proton beam mainly results in isolated, mostly repairable DNA breaks, the extremely localized emission of high-LET radiation produced by the proton-boron fusion in the Bragg peak region causes irreparable clustered DNA damage, similar in nature to that induced by 12C ions, hence the expected increase in effectiveness at tumor cell killing.