Multicellular dosimetry for micrometastases: dependence of self-dose versus cross-dose to cell nuclei on type and energy of radiation and subcellular distribution of radionuclides.

TLDR

Radioimmunotherapy typically uses beta‑emitting radionuclides to treat large tumors, but for eradicating small cancer clusters, Auger electrons or alpha particles are preferred because they deposit energy locally. The authors modeled how internalized radionuclides deliver dose to cell nuclei, showing that self‑dose dominates for Auger emitters while cross‑dose from neighboring cells becomes significant for beta or alpha emitters, especially as cluster size grows. They found that Auger emitters always generate a substantial self‑dose, whereas when self‑dose is negligible the mean nuclear dose equals the mean dose to the micrometastasis.

Abstract

In radioimmunotherapy, the treatment of bulk tumors by radionuclides that emit energetic beta particles is the preferred approach. However, for the eradication of small clusters of cancer cells, radionuclides that emit Auger electrons or alpha particles are considered to be advantageous because of their ability to deposit radiation energy locally. If such radionuclides are internalized by the cells, the total dose to the cell nuclei is thought to be primarily determined by the self-dose (dose to cell nucleus from activity within the cell) in comparison to the cross-dose (dose to the cell nucleus from activity in all other cells). Model calculations were also performed for several radionuclides (Auger, beta and alpha emitters). Absorbed fractions for sources of monoenergetic electron and alpha particles, distributed uniformly in small spheres (26-5000 microns), were also calculated along with S-values for a number of radionuclides.When most of the cells in the cluster are labeled with beta or alpha emitters, the cross-dose component of the total dose is important irrespective of cluster size and subcellular source distribution and increases as the cluster size increases. The self-dose is always important for Auger emitters. When the self-dose is negligible, the mean absorbed dose to the cell nuclei is well represented by the mean dose to the micrometastasis.