Non-specific cellular biomolecules and DNA within the beta-radiation field

Non-specific cellular biomolecules and DNA within the beta-radiation field represent the collective physical and chemical targets of beta-emitting radiopharmaceuticals. When these radionuclides decay, they emit high-energy electrons (beta particles) that traverse a finite range in biological tissue, typically between 1 and 10 millimeters (IAEA, 2021). Within this range, the particles transfer energy to cellular components through two primary mechanisms: direct ionization of the DNA phosphate backbone and indirect damage via the radiolysis of water, which generates highly reactive hydroxyl radicals (National Cancer Institute, 2023). These processes result in complex DNA lesions, including double-strand breaks that are difficult for the cell to repair, as well as the oxidation of proteins and lipids. The accumulation of such damage disrupts essential biological functions, leading to cell cycle arrest, mitotic catastrophe, and programmed cell death or apoptosis (Sgouros et al., 2020). This mechanism is therapeutically exploited in oncology to destroy malignant cells while sparing distant healthy tissues, although it necessitates careful dosing to manage toxicities to adjacent organs within the radiation path. Common drugs utilizing this target include Lutetium-177 based therapies like Pluvicto and Lutathera, which deliver localized radiation to specific tumor sites (FDA, 2022).

Other names

Cellular DNACytoplasmic biomoleculesIonizing radiation targetsRadiolytic targetsGenomic DNA and cellular proteins within the ionization path

Emission of high-energy beta particles (electrons) that cause direct ionization of the DNA phosphate backbone and indirect damage via the production of reactive oxygen species (ROS) through water radiolysis, leading to lethal double-strand breaks and cellular apoptosis (Sgouros et al., 2020; IAEA, 2021).