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Measurement of the spatial dose distribution in organs and tumors is needed to inform treatment dose prescription and reduce off-target toxicity, at not only organ but also sub-organ scales. Digital autoradiography with $$\\upalpha$$<\/jats:tex-math>\n \u03b1<\/mml:mi>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula>-sensitive detection devices can measure radioactivity distributions at 20\u201340 $$\\upmu {\\hbox {m}}$$<\/jats:tex-math>\n \n \u03bc<\/mml:mi>\n m<\/mml:mtext>\n <\/mml:mrow>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula> resolution, but anatomical characterization is typically limited to 2D. We collected digital autoradiographs across whole tissues to generate 3D dose volumes and used them to evaluate the simultaneous tumor control and regional kidney dosimetry of a novel therapeutic radiopharmaceutical for prostate cancer, [225<\/jats:sup>Ac]Ac-Macropa-PEG4<\/jats:sub>-YS5, in mice. 22Rv1 xenograft-bearing mice treated with 18.5 kBq of [225<\/jats:sup>Ac]Ac-Macropa-PEG4<\/jats:sub>-YS5\u00a0were sacrificed at 24 h and 168 h post-injection for quantitative $$\\upalpha$$<\/jats:tex-math>\n \u03b1<\/mml:mi>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula>-particle digital autoradiography and hematoxylin and eosin staining. Gamma-ray spectroscopy of biodistribution data was used to determine temporal dynamics and $$^{213}$$<\/jats:tex-math>\n \n \n \n 213<\/mml:mn>\n <\/mml:mmultiscripts>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula>Bi\u00a0redistribution. Tumor control probability and sub-kidney dosimetry were assessed. Heterogeneous $$^{225}$$<\/jats:tex-math>\n \n \n \n 225<\/mml:mn>\n <\/mml:mmultiscripts>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula>Ac\u00a0spatial distribution was observed in both tumors and kidneys. Tumor control was maintained despite heterogeneity if cold spots coincided with necrotic regions. $$^{225}$$<\/jats:tex-math>\n \n \n \n 225<\/mml:mn>\n <\/mml:mmultiscripts>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula>Ac\u00a0dose-rate was highest in the cortex and renal vasculature. Extrapolation of tumor control suggested that kidney absorbed dose could be reduced by 41% while maintaining 90% TCP. The 3D dosimetry methods described allow for whole tumor and organ dose measurements following $$^{225}$$<\/jats:tex-math>\n \n \n \n 225<\/mml:mn>\n <\/mml:mmultiscripts>\n <\/mml:math><\/jats:alternatives><\/jats:inline-formula>Ac\u00a0radiopharmaceutical therapy, which correlate to tumor control and toxicity outcomes.<\/jats:p>","DOI":"10.1038\/s41598-024-70417-3","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T07:03:53Z","timestamp":1724828633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["3D small-scale dosimetry and tumor control of 225Ac radiopharmaceuticals for prostate cancer"],"prefix":"10.1038","volume":"14","author":[{"given":"Robin","family":"Peter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil P.","family":"Bidkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kondapa Naidu","family":"Bobba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luann","family":"Zerefa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrashekhar","family":"Dasari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan","family":"Meher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Wadhwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Oskowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Vetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Flavell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngho","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"70417_CR1","doi-asserted-by":"publisher","first-page":"17588359","DOI":"10.1177\/17588359231157632","volume":"15","author":"A Jang","year":"2023","unstructured":"Jang, A., Kendi, A. & Sartor, O. 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