Experimental designs for radiobiological characterization of an accelerator-based BNCT system in preclinical studies

Several types of accelerator-based boron neutron capture therapy (AB-BNCT) systems have been developed; however, the features of neutron beams differ among facilities depending on the target type and acceleration energy. AB-BNCT systems with both downward and horizontal beams have been developed. Preclinical evaluation of AB-BNCT is an important prerequisite for its use as basic data for clinical trials. Herein, we describe a general scheme for evaluating the safety and efficacy of BNCT systems.

Cell-based assays and animal model studies were designed to assess the safety and efficiency of BNCT for preclinical evaluation. For cell-based studies, particular types of cancer and normal cells can be used depending on the planning of clinical trial designs. For animal studies, small rodents can only be used, depending on the medical regulations of countries.

The preclinical experimental designs were found necessary to include following conditions; 1) The radioactivation level of animals after neutron beam irradiation is necessary to confirm in order to transfer the animals to outside facilities for long-term observations. 2) For each AB-BNCT system, determination of the value of the relative biological effect (RBE) of the neutron (hydrogen) dose, which is the dose from elastic scattering of fast and epithermal neutrons on cellular and tissue hydrogens, is necessary. 3) Cytotoxicity and genotoxicity in the absence and presence of boron drugs should be tested by assessing cell survival and micronuclei formation, respectively. 4) In animal models, local and systemic toxicities, including hematological profiles, should be evaluated in the acute and long-term phases. 5) A stable setup for irradiation geometry with optimized shielding materials for the neutron beam is also necessary.

We confirmed that the designed preclinical experimental models are useful for evaluating the safety and efficacy of the AB-BNCT system from a biological perspective.