Radiation doses to the cell nucleus in single cells and cells in micrometastases in targeted therapy with (131)I labeled ligands or antibodies

PURPOSE: The aim of this study was to theoretically investigate how the radiation dose to cell nuclei depends on the subcellular position of (131)I. The influence of the size of the cells and crossfire irradiation in clusters of cells was also studied. METHODS AND MATERIAL: Using data describing the dose rate around a point source of (131)I, we calculated the dose distributions inside and around cell models of different sizes. The assumed positions of (131)I were on the cellular or nuclear membrane, in the cytoplasm, in the nucleus, or spread in the whole cell. The mean doses to the nucleus of the targeted cell and to the nuclei of its neighbors were calculated using the dose distributions. RESULTS: The dose distributions inside a single targeted cell showed very different distribution profiles depending on the subcellular position of the (131)I. Targeting the nucleus instead of the cellular membrane could increase the dose to the nucleus 10-fold. Crossfire irradiation can be the major contributor to the nuclear dose in clusters of more than six cells. CONCLUSIONS: Dosimetry without microscopic considerations is inadequate for targeted radionuclide therapy of disseminated or clustering tumor cells exposed to (131)I. Therapeutic doses could be achieved, even in single cells, when (131)I was positioned near, or inside the cell nucleus, or when the clusters were large enough.