Radiobiological studies for improving the treatment planning of Neutron Capture Therapy

Resumen

Theoretical and experimental analyses of the neutron biological damage associated with Boron Neutron Capture Therapy has been performed, both with the objective of improving the treatment planning regimes. A formalism is presented that combines the simplicity of the currently used one with the accuracy of the iso-effective one. This formalism includes the use of the linear quadratic model as well as the deployment of new weighting factors that are independent of dose and survival. In addition, a theoretical calculation of the individual effects of each secondary particle resulting from the neutron interaction with the tissue is given. This calculation shows how the weighting factors depend heavily on the neutron energy and should not be considered as currently the same for thermal and epithermal neutrons. Finally, a series of in vitro irradiation experiments have been carried out in order to obtain neutron radiobiological data. Six cell lines with interest in BNCT have been irradiated at three different facilities: the Institut Laue-Langevin (Grenoble), the Centro Nacional de Aceleradores (CNA, Sevilla) and the Virgen de las Nieves Hospital (Granada). Experiments at the cold neutron beam at Institut Laue-Langevin were performed in order to establish the effect of low energy neutrons without the influence of epithermal neutrons and with a minimal influence from the effects of photons. In this beam, two other experiments have been carried out: one in order to study the effect of the boron compound BPA (Boron phenylalanine) in different cell lines, and the other one in order to isolate the effect of neutron capture by nitrogen as well as that of the effect of the gammas produced by the beam. This last experiment used nitrogen isotope labeling and has been received as an innovative approach in this field. The other two irradiation experiments, using epithermal neutrons at the Centro Nacional de Aceleradores and using photons in a hospital accelerator, gives values for other more energetic neutrons and for the reference radiation. In all the experiments cell survival was studied after irradiation with clonogenic and colorimetric assays. Overall, these experiments provide data of the biological effect after in vitro irradiation for the different dose components involved in BNCT irradiation: namely thermal, epithermal, boron and photons. The weighting factors (RBE factors) for each of the dose component and cell line has been obtained. The influence of the type of dose chosen as the reference dose has also been studied. The data for these different irradiations gives information about the damage in different type of tumor and healthy cells; this is knowledge that may be of value for future BNCT treatments.