ABSTRACT

Dosimetry plays an important role in understanding and predicting the response of tumors and normal tissues to radiopharmaceuticals. The spatial scales over which dosimetry is performed for radiopharmaceuticals range from nanometers to centimeters, depending on the application. This chapter focusses on radiation dosimetry at the cellular and multicellular scales which span generally from micrometers to millimeters. The distribution of radiopharmaceuticals is typically highly nonuniform at this spatial scale, with some cells taking up substantial amounts of the radiopharmaceutical while others accumulate little to none. Depending on the type and range of the radiations emitted (alpha particles, beta particles, Auger electrons) by the radiopharmaceutical, this can have a substantial effect on the spatial distribution of absorbed dose and corresponding biological responses. The biological effect of the radiations emitted can also depend on the location of the radioactive decay within the cell (e.g., nucleus vs. cytoplasm). Accordingly, the response of a given cell depends on the absorbed dose received from radiations emitted by decays within the cell (self-dose) and radiations emitted by decays in neighbour cells (cross-dose), among other factors. This chapter reviews the evolution of the various approaches that have been taken to calculate absorbed dose at the cellular and multicellular levels, and how these calculations have been used to predict biologic effect. Several examples are worked out for the interested reader to demonstrate how the software application MIRDcell, a free software application, can be used to calculate absorbed doses to single cells, cells organized on a planar surface, or cells organized in three dimensional clusters, and predict the surviving fraction of the cell population. This software tool can be used for both research and educational purposes.