{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T03:08:19Z","timestamp":1779073699217,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Prostate\u2010specific membrane antigen (PSMA) is overexpressed in over 90% of prostate cancer tumors, making it a strong target for imaging and therapy. The diagnostic tracer [\n                    <jats:sup>18<\/jats:sup>\n                    F]F\u2010Piflufolastat provides high affinity and image quality, while the \u03b2\u2010emitter [\n                    <jats:sup>177<\/jats:sup>\n                    Lu]Lu\u2010PSMA\u2010617 enables targeted treatment. Despite differences in radioactive half\u2010life, their shared PSMA\u2010binding and pharmacokinetic profiles suggest potential for translational pharmacokinetic modeling. We hypothesized that the published full\u2010body physiologically based pharmacokinetic (PBPK) model could be directly translated across the investigated PSMA ligands to predict tracer distribution within the same patient. A PBPK model was developed by rebuilding and modifying a published [\n                    <jats:sup>68<\/jats:sup>\n                    Ga]Ga\u2010PSMA\u201011\/[\n                    <jats:sup>177<\/jats:sup>\n                    Lu]Lu\u2010PSMA\u2010617 model to simulate [\n                    <jats:sup>18<\/jats:sup>\n                    F]F\u2010Piflufolastat PK. Patient\u2010specific factors included tumor volume, PSMA receptor density, organ blood flow, and renal clearance. Verification used published data, dynamic positron emission tomography (PET) from eight patients, and static total\u2010body PET\/computed tomography (CT) at 2\u2009h from five patients. Extrapolation to [\n                    <jats:sup>177<\/jats:sup>\n                    Lu]Lu\u2010PSMA\u2010617, using fitted receptor density, was evaluated against 24\u2010h and 7\u2010day Single\u2010Photon Emission Computed Tomography (SPECT) data from two patients using mean prediction error (PE). The model accurately predicted [\n                    <jats:sup>18<\/jats:sup>\n                    F]F\u2010Piflufolastat tumor uptake (median PE \u22123.44% (IQR \u22123.79 to \u22123.17) and \u22123.53% (IQR \u22123.78 to \u22123.00) in internal and external cohorts) and showed consistency with 7\u2010day [\n                    <jats:sup>177<\/jats:sup>\n                    Lu]Lu\u2010PSMA\u2010617 SPECT observations. However, predictions for other organs were variable (median PE ranging between \u221289.7 and 144), indicating limitations of a one\u2010to\u2010one molecular translational approach. These findings demonstrate that PBPK modeling can capture key determinants of PSMA tracer distribution, and link [\n                    <jats:sup>18<\/jats:sup>\n                    F]F\u2010Piflufolastat imaging to [\n                    <jats:sup>177<\/jats:sup>\n                    Lu]Lu\u2010PSMA\u2010617 predictions. However, improved representation of systemic and organ\u2010level kinetics is required. Future work should explore a limited PBPK approach, focusing on accurate blood kinetics and organ\u2010specific modeling.\n                  <\/jats:p>","DOI":"10.1111\/cts.70583","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T12:29:51Z","timestamp":1778848191000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leveraging [\n                    <scp>\n                      <sup>18<\/sup>\n                      F\n                    <\/scp>\n                    ]F\u2010Piflufolastat\n                    <scp>PET<\/scp>\n                    for\n                    <scp>PBPK<\/scp>\n                    Prediction of Tissue Distribution and Therapy Optimization in Prostate Cancer"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-7409","authenticated-orcid":false,"given":"Suzanne","family":"van der Gaag","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0308-7060","authenticated-orcid":false,"given":"Mike J. C.","family":"Veerman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habibe","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Amsu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian J. V.","family":"Pruijn","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-2305","authenticated-orcid":false,"given":"Daniela E.","family":"Oprea\u2010Lager","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"},{"name":"Department of Medical Imaging Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5946-0173","authenticated-orcid":false,"given":"Matthijs C. F.","family":"Cysouw","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-145X","authenticated-orcid":false,"given":"Bernard H. E.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Urology, Prostate Cancer Network Amsterdam Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-740X","authenticated-orcid":false,"given":"Maqsood M.","family":"Yaqub","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3419-3368","authenticated-orcid":false,"given":"Andr\u00e9 N.","family":"Vis","sequence":"additional","affiliation":[{"name":"Department of Urology, Prostate Cancer Network Amsterdam Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-5391","authenticated-orcid":false,"given":"Harry","family":"Hendrikse","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"},{"name":"Department of Hospital Pharmacy Erasmus MC, University Medical Center  Rotterdam GD the Netherlands"},{"name":"Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center  Rotterdam GD the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-3407","authenticated-orcid":false,"given":"Imke H.","family":"Bartelink","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, Imaging and Biomarkers  Amsterdam the Netherlands"},{"name":"Department of 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