{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:04:40Z","timestamp":1788404680171,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG","award":["502536527"],"award-info":[{"award-number":["502536527"]}]},{"name":"DFG","award":["GL 236\/15-1"],"award-info":[{"award-number":["GL 236\/15-1"]}]},{"name":"DFG","award":["KO 4966\/5-1"],"award-info":[{"award-number":["KO 4966\/5-1"]}]},{"name":"DFG","award":["SCHI 1372\/5-1"],"award-info":[{"award-number":["SCHI 1372\/5-1"]}]},{"name":"Bavarian Cancer Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Accurate absorbed dose estimation is essential for optimising targeted radionuclide therapy (TRT) in metastatic castration-resistant prostate cancer, where kidney toxicity is dose-limiting. [177Lu]Lu-rhPSMA-10.1 is a novel PSMA-targeted radioligand with favourable tumour-to-kidney uptake ratios; however, inter-patient pharmacokinetic variability can lead to differences in organ and tumour absorbed doses under fixed-activity administration. Personalised dosimetry offers a means to address this variability. This work aims to create mouse PBPK model-based digital twins for [177Lu]Lu-rhPSMA-10.1 to test the model\u2019s resistance to noise and evaluate its impact on accuracy and absorbed dose calculations. Methods: Five CB-17 SCID mice bearing LNCaP tumour xenografts received 2.6\u20133.1 MBq [177Lu]Lu-rhPSMA-10.1 intravenously. Biodistribution was assessed 24 h post-injection by organ weighing and gamma counting. The PBPK model, implemented in MATLAB SimBiology (R2023a), was fitted to individual biodistribution data using mouse-specific physiological parameters. Digital twins\u2014combining the model with fitted parameters\u2014were used to generate time\u2013activity curves (TACs) for kidneys, tumours, and the whole body. Gaussian noise (\u03c3 = 0\u20130.35) was added to TACs to simulate measurement error. The model was refitted, and absorbed doses from time-integrated activities (TIAs) were compared to digital twin references. Results: The digital twin approach reproduced experimental data with physiologically plausible parameters. Absorbed dose estimates remained consistent and robust, deviating by &lt;2.3% in kidneys and &lt;1.0% in tumours. Conclusions: PBPK-based digital twins enable reliable, individualised dosimetry, even under substantial measurement uncertainty.<\/jats:p>","DOI":"10.3390\/cancers17243957","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:17:27Z","timestamp":1765451847000},"page":"3957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Digital Twins for Radiopharmaceutical Dosimetry: PBPK Modelling of [177Lu]Lu-rhPSMA-10.1 in a Preclinical mCRPC Model"],"prefix":"10.3390","volume":"17","author":[{"given":"Gustavo","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"},{"name":"Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8675-9306","authenticated-orcid":false,"given":"Elham","family":"Yousefzadeh-Nowshahr","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"},{"name":"Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5989-5609","authenticated-orcid":false,"given":"Valentina","family":"Vasic","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"},{"name":"Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Central Institute for Translational Cancer Research (TranslaTUM), Technical University Munich, 81675 Munich, Germany"},{"name":"Department of Nuclear Medicine, TUM University Hospital, TUM School of Medicine and Health, Bavarian Cancer Research Center (BZKF), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5530-6264","authenticated-orcid":false,"given":"Luca","family":"Nagel","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, TUM University Hospital, TUM School of Medicine and Health, Bavarian Cancer Research Center (BZKF), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wurzer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, TUM University Hospital, TUM School of Medicine and Health, Bavarian Cancer Research Center (BZKF), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-4628","authenticated-orcid":false,"given":"Franz","family":"Schilling","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, TUM University Hospital, TUM School of Medicine and Health, Bavarian Cancer Research Center (BZKF), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-7806","authenticated-orcid":false,"given":"Ambros","family":"Beer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, TUM University Hospital, TUM School of Medicine and Health, Bavarian Cancer Research Center (BZKF), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-1782","authenticated-orcid":false,"given":"Susanne","family":"Kossatz","sequence":"additional","affiliation":[{"name":"Central Institute for Translational Cancer Research (TranslaTUM), Technical University Munich, 81675 Munich, Germany"},{"name":"Department of Nuclear Medicine, TUM University Hospital, TUM School of Medicine and Health, Bavarian Cancer Research Center (BZKF), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-1576","authenticated-orcid":false,"given":"Gerhard","family":"Glatting","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"},{"name":"Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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