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Due to the increasing clinical application of alpha particles, accurate assessment of their dosimetry at the cellular scale should be strongly advocated. Although observations of the impact of cell and nuclear geometry have been previously reported, this effect has not been fully quantified. Additionally, alpha particle dosimetry presents several challenges and most conventional methodologies have poor resolution and are limited to average parameters across populations of cells. Meaningful dosimetry studies with alpha particles require detailed information on the geometry of the target at a subcellular scale.  Methods . The impact of cellular geometry was evaluated for 3 different scenarios, a spherical cell with a concentric nucleus, a spherical cell with an eccentric nucleus and a model of a cell attached to a flask, consisting of a hemispherical oblate ellipsoid, all exposed to 1,700  211 At radionuclide decays. We also evaluated the cross-irradiation of alpha particles as function of distance to a source cell. Finally, a nanodosimetric analysis of absorbed dose to the nucleus of a cell exposed to 1 Gy of different alpha emitting radionuclides was performed.  Results . Simulated data shows the dosimetry of self-absorbed-dose strongly depends on activity localization in the source cell, but that activity localization within the source cell did not significantly affect the cross absorbed dose even when cells are in direct contact with each other. Additionally, nanodosimetric analysis failed to show any significant differences in the energy deposition profile between different alpha particle emitters.  Conclusions . The collected data allows a better understanding of the dosimetry of alpha particles emitters at the sub-cellular scale. Dosimetric variations between different cellular configurations can generate complications and confounding factors for the translation of dosimetric outcomes into clinical settings, but effects of different radionuclides are generally similar.

TOPAS a tool to evaluate the impact of cell geometry and radionuclide on alpha particle therapy