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These include higher linear energy transfer (LET) and shorter ranges, which enhance localized cell killing while minimizing off\u2010target effects. While these radionuclides induce DNA damage both in source\u2010cells and neighboring cells (crossfire effect), their distinct radiation profiles provide critical metrics to compare their therapeutic efficacy. By quantifying these differences, especially in micrometastatic settings, the optimal radionuclide for specific clinical scenarios could be selected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      This Study aims to develop a comprehensive pipeline based on Monte Carlo (MC) simulations to compare the therapeutic efficacy of\n                      <jats:sup>225<\/jats:sup>\n                      Ac,\n                      <jats:sup>177<\/jats:sup>\n                      Lu, and\n                      <jats:sup>161<\/jats:sup>\n                      Tb in the treatment of mCRPC based on clinically administered activity (7.4 GBq for\n                      <jats:sup>177<\/jats:sup>\n                      Lu,\n                      <jats:sup>161<\/jats:sup>\n                      Tb, and 7 MBq for\n                      <jats:sup>225<\/jats:sup>\n                      Ac) in a multi\u2010cell model. Besides evaluating the absorbed dose at the cellular level, the Biological Effect Cell Kernel (BECK) method is proposed to compare the radiobiological effect of radionuclides, accounting for the crossfire effect using 3D convolution.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 2\u00a0\u00b5m resolution cell model was constructed with a 20\u00a0\u00b5m cell, an 8\u00a0\u00b5m nucleus diameter, and a 26\u00a0\u00b5m center\u2010to\u2010center distance. This configuration resulted in a cellular fraction of 0.24\u00a0mL\/g, in agreement with that estimated from six prostate cancer patients using CT Perfusion. The prostate time\u2010integrated activity (TIA) in the model was estimated from a patient based on a dynamic 300 MBq\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010DCFPyL PET scan after scaling to account for the higher administered activity in therapy. The TOPAS\u2010nBio MC tool was used to calculate the absorbed dose and the DNA breaks in the cell model. To account for the crossfire effect, we created the BECK, an isotropic 3D kernel, demonstrating the DNA breaks in the source\u2010containing cell, and those induced in its neighboring cells. The BECK was convolved with the 3D TIA maps of the cell model to obtain the DNA break maps.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cellular absorbed dose was higher than the macro\u2010scale dose based on SPECT\u2010derived TIA, by 31.3%, 15.7%, and 39.8% for\n                      <jats:sup>225<\/jats:sup>\n                      Ac,\n                      <jats:sup>177<\/jats:sup>\n                      Lu, and\n                      <jats:sup>161<\/jats:sup>\n                      Tb, respectively. At the single\u2010cell level,\n                      <jats:sup>225<\/jats:sup>\n                      Ac induced markedly higher DNA breaks per source \u2013 48 double\u2010strand breaks (DSBs), and 32 complex DSBs, compared to\n                      <jats:sup>177<\/jats:sup>\n                      Lu \u2013 0.022 and 0.017, and\n                      <jats:sup>161<\/jats:sup>\n                      Tb \u2013 0.083 and 0.073, respectively. Crossfire effects were dominant for\n                      <jats:sup>255<\/jats:sup>\n                      Ac and\n                      <jats:sup>177<\/jats:sup>\n                      Lu at \u223c75% and less pronounced for\n                      <jats:sup>161<\/jats:sup>\n                      Tb at \u223c41%. The maximum ranges at which 99.99% of the total DNA breaks were observed were approximately 85\u00a0\u00b5m for\n                      <jats:sup>225<\/jats:sup>\n                      Ac, 150\u00a0\u00b5m for\n                      <jats:sup>177<\/jats:sup>\n                      Lu, and 110\u00a0\u00b5m for\n                      <jats:sup>161<\/jats:sup>\n                      Tb.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      DPKs and BECKs of\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>2<\/jats:sup>\n                      \u2075Ac, \u00b9\u2077\u2077Lu, and \u00b9\u2076\u00b9Tb were developed to quantify cellular\u2010level dose distributions and biological efficacy, revealing micrometer\u2010scale heterogeneity accentuated by short\u2010range emissions (\u03b1, CEs, AEs). Results demonstrate \u00b9\u2076\u00b9Tb's optimal performance for micrometastases\u2014surpassing \u00b9\u2077\u2077Lu's efficacy with lower toxicity than\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>2<\/jats:sup>\n                      \u2075Ac\u2014while relative biological effectiveness predicts activity requirements:\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>2<\/jats:sup>\n                      \u2075Ac\u00a0&lt;&lt;\u00a0\u00b9\u2076\u00b9Tb\u00a0&lt;\u00a0\u00b9\u2077\u2077Lu.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.18035","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T04:39:39Z","timestamp":1754714379000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Framework to calculate\n                    <sup>225<\/sup>\n                    Ac,\n                    <sup>177<\/sup>\n                    Lu, and\n                    <sup>161<\/sup>\n                    Tb radiation dose and biological effect in metastatic castration\u2010resistant prostate cancer treatment"],"prefix":"10.1002","volume":"52","author":[{"given":"Shahin","family":"Ghaseminejad","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics Western University  London Ontario Canada"},{"name":"Imaging Program Robarts Research Institute and Lawson Research Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"De Sarno","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics Western University  London Ontario Canada"},{"name":"Imaging Program Robarts Research Institute and Lawson Research Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Bauman","sequence":"additional","affiliation":[{"name":"Department of 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