{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:04:50Z","timestamp":1784192690054,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Novel, radiohybrid, beta-particle-emitting, PSMA-targeted radiopharmaceutical therapy [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-rhPSMA-10.1 shows promising preclinical and clinical efficacy in prostate cancer. Here, we evaluated [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-rhPSMA-10.1 as a potential alpha-particle-emitting, PSMA-targeted radiopharmaceutical therapy for prostate cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Lipophilicity of [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-rhPSMA-10.1 and [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-rhPSMA-10.1 (0.1-0.3 MBq) was assessed by shake-flask method. PSMA-binding affinity (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) was evaluated in a competitive binding assay using rhPSMA-10.1 complexed with natural Lanthanum ([\n                      <jats:sup>nat<\/jats:sup>\n                      La]; non-radioactive [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac surrogate) or natural Lutetium ([\n                      <jats:sup>nat<\/jats:sup>\n                      Lu]) in PSMA-expressing LNCaP cells. Cellular internalization (normalized to that of [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-PSMA-I&amp;amp;T) was assessed after 1-hour incubation of LNCaP cells (5x10\n                      <jats:sup>5<\/jats:sup>\n                      cells in 1 mL\/well) with [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-rhPSMA-10.1 or [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-rhPSMA-10.1.\n                      <jats:italic>In vivo<\/jats:italic>\n                      assessments were conducted using PSMA-expressing 22Rv1 prostate cancer xenografts (eight mice\/group plus untreated controls). Efficacy (tumour growth and survival) versus controls was assessed \u226449 days after a single-dose of [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-rhPSMA-10.1 (30 KBq) or [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-rhPSMA-10.1 (30 MBq). Tolerability was evaluated by bodyweight monitoring.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-rhPSMA-10.1 and [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-rhPSMA-10.1 showed similar\n                      <jats:italic>in vitro<\/jats:italic>\n                      profiles: low lipophilicity (log D\n                      <jats:sub>oct\/PBS pH 7.4<\/jats:sub>\n                      = -3.4\u00a0\u00b1\u00a00.2 and log D\n                      <jats:sub>oct\/PBS pH 7.4<\/jats:sub>\n                      = -3.8\u00a0\u00b1\u00a00.1, respectively), high PSMA binding affinity ([\n                      <jats:sup>nat<\/jats:sup>\n                      La]La-rhPSMA-10.1 IC\n                      <jats:sub>50<\/jats:sub>\n                      \u00a0=\u00a03.6\u00a0\u00b1\u00a00.6 nM, [\n                      <jats:sup>nat<\/jats:sup>\n                      Lu]Lu-rhPSMA-10.1 IC\n                      <jats:sub>50<\/jats:sub>\n                      \u00a0=\u00a01.6\u00a0\u00b1\u00a00.1 nM) and high internalization (99%\u00a0\u00b1\u00a014 and 108%\u00a0\u00b1\u00a05, respectively).\n                      <jats:italic>In vivo<\/jats:italic>\n                      , [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-rhPSMA-10.1 significantly reduced tumour growth versus controls from Day 14-31 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05), and significantly prolonged median survival (43.5 days) versus controls (27.0 days;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.006). There were no significant differences in tumour growth suppression or survival between the radiopharmaceuticals, and both were well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-rhPSMA-10.1 displayed similar\n                      <jats:italic>in vivo<\/jats:italic>\n                      properties to [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-rhPSMA-10.1 and similar efficacy in prostate cancer xenografts at lower administered radioactivity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1868487","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:26:11Z","timestamp":1784190371000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Actinium-225-rhPSMA-10.1 as a novel, alpha-particle-emitting therapy for prostate cancer: results of a preclinical evaluation"],"prefix":"10.3389","volume":"16","author":[{"given":"Caroline","family":"Foxton","sequence":"first","affiliation":[{"name":"Blue Earth Diagnostics Ltd","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Waldron","sequence":"additional","affiliation":[{"name":"Blue Earth Therapeutics Ltd","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wurzer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Technical 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Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"Veggerby Gr\u00f8nlund","sequence":"additional","affiliation":[{"name":"Minerva Imaging","place":["\u00d8lstykke, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Wikke Hallund","sequence":"additional","affiliation":[{"name":"Minerva Imaging","place":["\u00d8lstykke, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Blue Earth Therapeutics Ltd","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J 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