{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:05:18Z","timestamp":1782961518311,"version":"3.54.5"},"reference-count":22,"publisher":"IOP Publishing","issue":"11","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/page\/copyright"},{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"New Frontiers in Research Fund - Exploration","award":["NFRFE-2019-00128"],"award-info":[{"award-number":["NFRFE-2019-00128"]}]},{"name":"Discovery Grants from the Natural Sciences and Engineering Research Council of Canada,","award":["RGPIN-2022-03887"],"award-info":[{"award-number":["RGPIN-2022-03887"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Phys. Med. Biol."],"published-print":{"date-parts":[[2025,6,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>\n                  <jats:italic>Objective.<\/jats:italic> Targeted Alpha Therapy (TAT) is a promising approach for treating metastatic cancers, utilizing alpha-emitting radionuclides conjugated to tumor-targeting molecules. Actinium-225 (<jats:sup>225<\/jats:sup>Ac) has emerged as a clinically relevant candidate due to its decay chain, which produces four successive alpha emissions, effectively damaging cancer cells. However, the nuclear recoil effect can lead to off-target redistribution of decay daughters, complicating dosimetry and increasing potential toxicity. This study aims to address these challenges by developing a direct alpha spectroscopy method for <jats:italic>in vitro<\/jats:italic> investigations of <jats:sup>225<\/jats:sup>Ac radiopharmaceuticals. <jats:italic>Approach.<\/jats:italic> We developed the Bio-Sample Alpha Detector (BAD), a silicon-based detector designed to operate under ambient conditions, enabling direct alpha spectroscopy of cell samples. AR42J rat pancreatic tumor cells, which express somatostatin receptor 2 (SSTR2), were incubated with [<jats:sup>225<\/jats:sup>Ac]Ac-crown-TATE, [<jats:sup>225<\/jats:sup>Ac]Ac-PSMA-617, and [<jats:sup>225<\/jats:sup>Ac]Ac<jats:sup>3+<\/jats:sup>. The BAD setup allowed radiolabeled cell samples to be positioned within 100 <jats:italic>\u00b5<\/jats:italic>m of the detector for alpha spectra acquisition with statistical uncertainties of less than 1% in count rates. Geant4 Monte Carlo simulations were employed to validate the experimental results. <jats:italic>Main results.<\/jats:italic> Distinct spectral differences between radiolabeled cells and reference samples confirmed the uptake of [<jats:sup>225<\/jats:sup>Ac]Ac-crown-TATE by AR42J cells. Detection of <jats:sup>213<\/jats:sup>Po, a decay daughter of <jats:sup>225<\/jats:sup>Ac, indicated partial retention and release of decay products from cells, providing insight into intracellular retention and radionuclide redistribution. Geant4 simulations confirmed the alignment of experimental data with theoretical predictions. <jats:italic>Significance.<\/jats:italic> This study introduces a novel method for directly measuring the behavior of <jats:sup>225<\/jats:sup>Ac and its decay daughters in biological samples using alpha spectroscopy. The BAD setup provides a valuable tool for investigating radionuclide retention, redistribution, and microdosimetry in radiopharmaceutical research.<\/jats:p>","DOI":"10.1088\/1361-6560\/add987","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T22:55:16Z","timestamp":1747349716000},"page":"115019","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel direct alpha spectroscopy technique for <sup>225<\/sup>Ac radiopharmaceutical detection in cancer cells"],"prefix":"10.1088","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5017-420X","authenticated-orcid":true,"given":"Mahsa","family":"Farasat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrad","family":"Saeedi Saghez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Wharton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9282-7976","authenticated-orcid":true,"given":"Sidney","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7667-4140","authenticated-orcid":true,"given":"Chris","family":"Vinnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6878-4086","authenticated-orcid":true,"given":"Madison","family":"Daignault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6965-4961","authenticated-orcid":true,"given":"Meghan","family":"Kostashuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4003-578X","authenticated-orcid":true,"given":"Nicholas","family":"Pranjatno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0179-082X","authenticated-orcid":true,"given":"Myla","family":"Weiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Andreoiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5842-4648","authenticated-orcid":false,"given":"Peter","family":"Kunz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"pmbadd987bib1","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/S0168-9002(03)01368-8","article-title":"Geant4\u2014a simulation toolkit","volume":"506","author":"Agostinelli","year":"2003","journal-title":"Nucl. 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All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2025-01-16","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-05-15","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-05-29","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}