Radiobiological effect of alpha particles. The scientific basis of targeted alpha-particle therapy

Targeted alpha therapy (TAT) uses alpha-emitting radionuclides to deliver high-energy radiation directly to a specific biological target. TAT has shown promising results in the treatment of advanced metastatic disease and has demonstrated greater efficacy than beta radiation in inducing apoptosis, mutations, carcinogenesis, chromosomal aberrations, and chromosomal instability. The biological effects of alpha particle radiation are associated with the high energy delivered over short distances, producing high levels of reactive oxygen and nitrogen species. Likewise, alpha particle radiation induces more mutations per median lethal dose compared to beta particles and promotes the accumulation of substitutions and indels. Identification of novel early response genes to alpha particles is critical for understanding the molecular mechanisms underlying genomic damage, cell death, and potentially latent malignant transformation. This review provides an overview of the biological effects of alpha particle exposure, with the aim of enhancing the understanding, research, and development of alpha-emitter-based radiopharmaceuticals. It also discusses anti-tumor immune responses, the induction of inflammatory cell death, alpha particle-cell membrane interactions, and the bystander effect. Dosimetry aspects were not covered in this review.