The Development of a Preclinical Alpha Irradiation Platform with Versatile Control of Dose, Dose Rate, and Spatiotemporal Irradiation Patterns

Abstract

Objectives. This study develops and validates a vacuum-based alpha irradiation platform to support preclinical radiobiology. We aim to demonstrate precise, independent control over incident energy, fluence rate, and spatiotemporal patterns, which are critical to the mechanisms underlying targeted alpha therapies and low-dose risk assessments. Approach. A vacuum-based system with a radioactive alpha source was designed and fabricated. The platform provides independent modulation of: (i) temporal patterns via a programmable gate valve; (ii) fluence rate across two orders of magnitude by varying source-to-aperture distance (57 to 381 mm); (iii) incident energy (0 to 4.6 MeV) using adjustable absorption layers; and (iv) spatial distributions via a 3D motion stage. Temporal precision was assessed via synchronized audio-electronic recordings. Fluence rates and energies were validated using CR-39 detectors and Monte Carlo (MC) simulations. Spatial precision was verified through programmed continuous and discrete trajectories. Main results. Validation experiments demonstrated high system fidelity. Measured irradiation durations deviated from programmed values by less than 0.3 s. Measured and computed fluence rates agreed within 3%. For energy validation, CR-39 track diameters matched MC model predictions within one standard deviation. Recorded spatial patterns and dimensions aligned well with programmed trajectories. Significance. We successfully validated a versatile vacuum-based platform that overcomes energy-degradation constraints of gas-filled systems. By providing multi-parametric control over alpha-particle delivery, this system enables systematic investigation into how energy, dose rate, and spatiotemporal patterns influence radiobiological responses. This platform is poised to optimize targeted alpha therapies and refine radiation protection frameworks.