The Auger electron dosimetry of indium-111 in mammalian cells in vitro

Most of the radionuclides used in the formulation of radiopharmaceuticals emit Auger electrons when they undergo radioactive decay. The release of these low-energy electrons at extracellular sites produces little direct damage to intracellular structures. However, many radiopharmaceuticals, or their metabolites, can be transported into the cell where the Auger electrons have the potential to damage nearby intracellular macromolecules, including DNA. In this preliminary study, chromosome damage, expressed as 60Co equivalent doses, and the effects on cell division following treatment with intracellular and extracellular 111In were measured in Chinese hamster V79 cells. The chromosome aberration yield in cells irradiated by intracellular 111In indicated that damage was induced at a rate of 7.2 X 10(-4) Gy/decay for levels of activity up to 0.075 Bq/cell and 4.5 X 10(4) and 2.9 X 10(4) Gy/decay for intermediate (0.204 Bq/cell) and high (0.389 Bq/cell) levels, respectively. Extracellular 111In-chloride produced damage at a rate of about 6.1 X 10(-12) Gy/decay. As little as 4.4 mBq/cell (about 4.4 X 10(3) Bq/ml of culture) of intracellular 111In was able to affect cell division, whereas extracellular 111In at 1.150 MBq/ml of culture had little effect. These data indicate that the Medical Internal Radiation Dose and International Committee on Radiation Units methods for organ dosimetry may underestimate the potential of intracellular Auger electron emitters to produce radiation damage.