Cell Irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences

Abstract

Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings. Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.

ICRP Publication 128: Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances

“…The assumption made here, that the absorbed dose is distributed uniformly within the cell, may result in underestimation of the risk. (28) This problem has been discussed in earlier publications (ICRP, 1979, 1991a, 2003), and by many other authors (e.g. Hofer, 1996; Gardin et al., 1999; Bingham et al., 2000; Feinendegen and Neumann, 2004). MIRD has given detailed advice and presented S values for the cellular level (Goddu et al., 1994, 1997).…”

Main Text

“…(28) This problem has been discussed in earlier publications (ICRP, 1979(ICRP, , 1991a(ICRP, , 2003, and by a large number of other authors, of which only a few are referred to here as an example (Hofer, 1996;Gardin et al, 1999;Bingham et al, 2000;Feinendegen and Neumann, 2004). MIRD has given detailed advice and presented S-values for the cellular level (Goddu et al, 1994(Goddu et al, , 1997.…”