In Vivo Accelerator-Based Boron Neutron Capture Therapy for Spontaneous Tumors in Large Animals: Case Series

(1) Background: accelerator-based neutron sources are a new frontier for BNCT but many technical issues remain. We aimed to study such issues and results in larger-animal BNCT (cats and dogs) with naturally occurring, malignant tumors in different locations as an intermediate step in translating current research into clinical practice. (2) Methods: 10 pet cats and dogs with incurable, malignant tumors that had no treatment alternatives were included in this study. A tandem accelerator with vacuum insulation was used as a neutron source. As a boron-containing agent, 10B-enriched sodium borocaptate (BSH) was used at a dose of 100 mg/kg. Animal condition as well as tumor progression/regression were monitored. (3) Results: regression of tumors in response to treatment, improvements in the overall clinical picture, and an increase in the estimated duration and quality of life were observed. Treatment-related toxicity was mild and reversible. (4) Conclusions: our study contributes to preparations for human BNCT clinical trials and suggests utility for veterinary oncology.

Application of a novel gas phase synthesis approach to carbonyl complexes of accelerator-produced 5d transition metals

In 2014 the first synthesis of a transactinide carbonyl complex – seaborgium hexacarbonyl – was reported. This was achieved in gas-phase chemical experiments in a beam-free environment behind the recoil separator GARIS. Extending this work to heavier elements requires more efficient techniques to synthesize carbonyl complexes as production rates of transactinide elements drop with increasing atomic number. A novel approach was thus conceived, which retains the benefit of a beam-free environment but avoids the physical preseparation step. The latter reduces the yields for products of asymmetric reactions such as those used for the synthesis of suitable isotopes of Sg, Bh, Hs and Mt. For this a series of experiments with accelerator-produced radioisotopes of the lighter homologues W, Re and Os was carried out at the tandem accelerator of JAEA Tokai, Japan. A newly developed double-chamber system, which allows for a decoupled recoil ion thermalization and chemical complex formation, was used, which avoids the low-efficiency physical preseparation step. Here, we demonstrate the feasibility of this newly developed method using accelerator-produced short-lived radioisotopes of the 5d homologues of the early transactinides.

A New Low-Energy Proton Irradiation Facility to Unveil the Mechanistic Basis of the Proton-Boron Capture Therapy Approach

Protontherapy (PT) is a fast-growing cancer therapy modality thanks to much-improved normal tissue sparing granted by the charged particles’ inverted dose-depth profile. Protons, however, exhibit a low biological effectiveness at clinically relevant energies. To enhance PT efficacy and counteract cancer radioresistance, Proton–Boron Capture Therapy (PBCT) was recently proposed. PBCT exploits the highly DNA-damaging α-particles generated by the p + 11B→3α (pB) nuclear reaction, whose cross-section peaks for proton energies of 675 keV. Although a significant enhancement of proton biological effectiveness by PBCT has been demonstrated for high-energy proton beams, validation of the PBCT rationale using monochromatic proton beams having energy close to the reaction cross-section maximum is still lacking. To this end, we implemented a novel setup for radiobiology experiments at a 3-MV tandem accelerator; using a scattering chamber equipped with an Au foil scatterer for beam diffusion on the biological sample, uniformity in energy and fluence with uncertainties of 2% and 5%, respectively, was achieved. Human cancer cells were irradiated at this beamline for the first time with 685-keV protons. The measured enhancement in cancer cell killing due to the 11B carrier BSH was the highest among those thus far observed, thereby corroborating the mechanistic bases of PBCT.

Concept and performance evaluation of two 3 GHz buncher units optimizing the dose rate of a novel preclinical proton minibeam irradiation facility

To demonstrate the large potential of proton minibeam radiotherapy (pMBRT) as a new method to treat tumor diseases, a preclinical proton minibeam radiation facility was designed. It is based on a tandem Van-de-Graaff accelerator providing a 16 MeV proton beam and a 3 GHz linac post-accelerator (designs: AVO-ADAM S.A, Geneva, Switzerland and ENEA, Frascati, Italy). To enhance the transmission of the tandem beam through the post-accelerator by a factor of 3, two drift tube buncher units were designed and constructed: A brazed 5-gap structure (adapted SCDTL tank of the TOP-IMPLART project (ENEA)) and a non-brazed low budget 4-gap structure. Both are made of copper. The performance of the two differently manufactured units was evaluated using a 16 MeV tandem accelerator beam and a Q3D magnetic spectrograph. Both buncher units achieve the required summed voltage amplitude of 42 kV and amplitude stability at a power feed of less than 800 W.

Measurement of the $$^{232}$$Th(n,f) cross section with quasi-monoenergetic neutron beams in the energy range 2–18 MeV

The fission cross section of $$^{232}$$ 232 Th has been measured at fast neutron energies, using a setup based on Micromegas detectors. The experiment was performed at the 5.5 MV Van de Graaff Tandem accelerator in the neutron beam facility of the National Centre for Scientific Research “Demokritos”. The quasi-monoenergetic neutron beams were produced via the $$^{3}$$ 3 H(p,n), $$^{2}$$ 2 H(d,n) and $$^{3}$$ 3 H(d,n) reactions, while the $$^{238}$$ 238 U(n,f) and $$^{235}$$ 235 U(n,f) reactions were used as references, in order to acquire cross-section data points in the energy range 2–18 MeV. The characterization of the actinide samples was performed via $$\alpha $$ α -spectroscopy with a Silicon Surface Barrier (SSB) detector, while Monte Carlo simulations with the FLUKA code were used to achieve the deconvolution of the $$^{232}$$ 232 Th $$\alpha $$ α peak from the $$\alpha $$ α background of its daughter nuclei present in the spectrum. Special attention was given to the study of the parasitic neutrons present in the experimental area, produced via charged particle reactions induced by the particle beam and from neutron scattering. Details on the data analysis and results are presented.

The Measurement of the Neutron Yield of the 7Li(p,n)7Be Reaction in Lithium Targets

A compact accelerator-based neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. An original design tandem accelerator is used to provide a proton beam. The neutron flux is generated as a result of the 7Li(p,n)7Be threshold reaction using the solid lithium target. A beam shaping assembly is applied to convert this flux into a beam of epithermal neutrons with characteristics suitable for BNCT. The BNCT technique is being tested in in vitro and in vivo studies, and dosimetry methods are being developed. Currently, the BNCT technique has entered into clinical practice in the world: after successful clinical trials, two clinics in Japan began treating patients, and four more BNCT clinics are ready to start operating. The neutron source proposed at the Budker Institute of Nuclear Physics served as a prototype for a facility created for a clinic in Xiamen (China). It is planned to equip the National Medical Research Center of Oncology (Moscow, Russia) and National Oncological Hadron Therapy Center (Pavia, Italy) with the same neutron sources. Due to the impending use of an accelerator neutron source for treating patients, the validation of the neutron yield of the 7Li(p,n)7Be reaction in lithium metal targets is required. The theoretical neutron yield has not been evaluated experimentally so far.