Towards Development of a Preclinical, Accelerator-Based Platform for Neutron Capture Therapy
Abstract
Purpose
Development of next-generation neutron capture therapy (NCT) agents demands rigorous preclinical testing to verify targeting efficacy, safety, and therapeutic gain under clinically relevant irradiation conditions. This work proposes a preclinical, accelerator-based neutron irradiation platform tailored to small animal treatments and in-vitro studies.
Methods
The proposed system leverages a commercially available cyclotron beamline and metaheuristically optimized beam shaping assembly (BSA). Micro-CT images of tumor-bearing mice were imported into MCNP and used as a reference for spectral fluence selection. Incident monoenergetic neutron energy was varied in sequential simulations, and dose was scored using the neutron KERMA approximation. Ratios between the average borated tumor dose and the 99th percentile of normal tissue dose were used to determine the neutron energy range of highest relative effect. Phase spaces for BSA design were generated with MCNP using a 16 MeV proton beam, and spectral yield was compared to experimental data. Candidate designs for the BSA were then produced through multi-objective optimization via NSGA-II, which assigned materials and dimensions for a parameterized geometry and evaluated designs based on spectrum and fluence rate objectives.
Results
The required neutron energy range for small animal NCT was identified (0.025-100 eV). After inclusion of spectral bounds within NSGA-II, multiple pareto optimal BSA designs achieved an estimated neutron flux of above 5x108 n/cm2/s. A subset of designs attained fluxes greater than 1x109 n/cm2/s at proton beam current of 100 μA. This corresponds to a tumor dose rate of over 10 Gy/hr when evaluating the system with the imported mouse geometries.
Conclusion
The proposed accelerator-based system will help advance the development of novel NCT agents. Additionally, this irradiator will support radiobiology studies and serve as a testbed for dosimetric measurements in neutron fields. Ongoing work comprises designing a monitoring chamber and treatment planning system, along with tuning accelerator beam parameters.