Abstract
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 211At 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.
Highlights
Alpha particle-based radionuclides have emerged as an attractive therapeutic option with increased clinical interest since the approval of 223RaCl2 in 2013, after the ALSYMPCA trial [1], as the first alpha emitting radionuclide for the treatment of metastatic castration resistant prostate cancer
The evaluation of cellular geometry showed an increased absorbed dose to the nucleus for the eccentric model when the activity is uniformly distributed on the cellular membrane or in the surrounding medium
Variation of 31%, when the cells are in direct contact with the source cell (0 μm), (figure 6(A)), and mean of 1.10 Gy and Standard Deviation (SD) of 0.75 Gy, and a coefficient of variation of 61% when the cell membranes are 20 μm away from the membrane of the source cell. In this situation ∼3% of cells do not absorb any dose. These values are in good agreement with MIRDcell simulations where cross-dose from cells exposed to the same activity at equivalent distances will have an absorbed dose of 6.78 Gy when cells are in direct contact with the source cell and 1.19 Gy when cell membranes are 20 μm away from the membrane of the source cell
Summary
Alpha particle-based radionuclides have emerged as an attractive therapeutic option with increased clinical interest since the approval of 223RaCl2 in 2013, after the ALSYMPCA trial [1], as the first alpha emitting radionuclide for the treatment of metastatic castration resistant prostate cancer (mCRPC). This has stimulated clinical interest in other alpha emitting radionuclides, such as astatine-211 (211At), actinium-225 (225Ac) and thorium-227 (227Th) in different clinical settings. Studying the effects of alpha particles at the sub-cellular level is of interest to determine the suitability of a given radionuclide for targeted radiotherapy., known as radiopharmaceutical therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
