DNA Double-Strand Break Induction via Targeted Alpha-Particle Emission (Targeted Alpha-Induced DSB)

DNA double-strand break (DSB) induction via targeted alpha-particle emission is a therapeutic strategy that leverages the high linear energy transfer (LET) of alpha particles to induce clustered DSBs within targeted cells. This mechanism is central to targeted alpha therapy (TAT), a form of radiopharmaceutical treatment designed to selectively destroy cancer cells while minimizing collateral damage to healthy tissue. The clustered DSBs overwhelm the cell’s repair machinery and frequently result in apoptosis (programmed cell death), senescence, or irreversible genomic instability if not properly repaired. Targeted Alpha Therapy exploits this mechanism by delivering alpha-emitting radionuclides directly to tumor sites using molecular carriers such as antibodies or peptides that bind specifically to cancer-associated antigens. The short range and high LET nature of alpha emissions ensure that cytotoxic effects are confined primarily to targeted cancerous tissues while sparing adjacent normal tissues.

Other names

Targeted Alpha Therapy (TAT)Alpha-Particle Induced DNA DamageRadionuclide Targeted DNA DamageAlpha-induced DSB

Localized induction of complex/clustered double-strand breaks in DNA by alpha-particle emission from targeted radionuclides, leading to cell death.