Polymersomes as nano-carriers to retain harmful recoil nuclides in alpha radionuclide therapy: A feasibility study

摘要

Targeted alpha therapy has shown promising preclinical and clinical results in the fight against cancer. The use of in vivo generators, generating a highly cytotoxic cascade of alpha particles, is attracting increasing interest for clinical application. ~(225)Ac is one of the nuclides that can serve as an in vivo generator. It is commercially available and provides four alpha particles with a total energy of 28 MeV per ~(225)Ac decay. However, its alpha emitting daughter nuclides may escape from the target region due to recoil and cause unwanted toxicity in other parts of the body. In this paper, we investigate the feasibility of designing spherical, block-copolymer based nano-carriers (polymersomes) to retain the recoiling daughter nuclides. A Monte Carlo code, called NANVES, has been developed to simulate the range distributions of recoil atoms in different materials and to determine the optimum nanocarriers design. Recoil ranges in planar polystyrene films were determined experimentally and compared to simulations of the experiment, indicating that NANVES may provide accurate results. Simulations of various nano-carriers designs indicate that double-layered polymersomes with a diameter of 800 nm are capable of completely retaining the first daughter nuclide 221Fr, while the escape fraction of the third radioactive daughter 213Bi is reduced to 20% and the percentage of alpha particles emitted from escaped daughter products outside the nano-carriers is less than 10%.