Cellular DNA and macromolecules

Cellular DNA and macromolecules within alpha-particle range represent the primary biological substrates for Targeted Alpha Therapy (TAT). Alpha particles are heavy, positively charged helium nuclei emitted by radionuclides such as Actinium-225 or Radium-223. Due to their high linear energy transfer (LET) and short tissue range, typically 50-100 micrometers, they deposit intense energy along a very narrow track (Nelson et al., 2021, Pharmaceutics). This energy deposition causes severe, often irreparable damage to the genomic DNA, specifically through complex double-strand breaks, as well as the oxidation of proteins and lipids within the cell (Sgouros et al., 2020, Nature Reviews Drug Discovery). This localized destruction is highly effective at killing cancer cells while minimizing damage to distant healthy tissues, provided the alpha-emitting isotope is accurately delivered to the tumor site. The high biological effectiveness of alpha radiation ensures that even a few hits to the cell nucleus can be sufficient to induce cell death via apoptosis or mitotic catastrophe (Parker et al., 2018, Journal of Nuclear Medicine).

Other names

Nuclear DNAGenomic DNACellular proteinsCellular lipidsRadiation targets

Alpha particles deliver high linear energy transfer (LET) radiation, causing dense ionization along a short path (50-100 micrometers). This results in complex, clustered double-strand DNA breaks (DSBs) and oxidative damage to proteins and lipids, leading to cell death (Kim & Han, 2018, Applied Sciences).