Capture-enhanced neutron irradiation to treat Alzheimer's disease: Design of a small animal set-up for future in-vivo experiments.

BACKGROUND

Alzheimer's disease (AD) is characterized by the accumulation of β $\beta$ -Amyloid and τ $\tau$ proteins in the brain that causes dementia. To date, there is no cure capable of eradicating AD, so it is necessary to study a performing therapy. The NECTAR project aims to investigate an extension of the conventional Boron Neutron Capture Therapy principles as a possible treatment for AD at different scales (protein, cells, animal).

PURPOSE: The present study focuses on a macroscopic scale and wants to propose an irradiation set-up for mice in the thermal column (TC) of the Triga Mark II reactor of Pavia University, in view of the forthcoming in vivo irradiation of healthy and transgenic AD mouse models.

METHODS

Monte Carlo simulations were carried out with the MCNP6 code to test different irradiation positions and study the least toxic treatment possible by modeling neutron shielding to preserve healthy tissue. A shielding prototype was built and tested by means of neutron activation measurements. A geometrical mouse model was developed with the aim of computing the dose-rates induced in each radiosensitive organ and thus to estimate possible irradiation times for future in vivo experiments.

RESULTS

The computational study showed that the safest irradiation condition involves placing the shielding 20 cm from the TC entrance and that the best performing shielding material is 6 Li $^{6}{\rm Li}$ enriched lithium carbonate. Furthermore, taking into account the tolerance doses of each organ, the maximum animal irradiation time in an AD context is 45 min. The proposed set-up could also be used for preclinical studies on brain tumors; in this context, the maximum estimated irradiation time is 11 min.

CONCLUSION

The proposed work is pivotal in the study of a possible treatment for AD in a neutron irradiation context, paving the way for the next phase of the NECTAR project involving in vivo irradiation of AD mouse models and thus making it possible to assess its efficacy and its possible future extension to the human brain.