{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:17:00Z","timestamp":1788617820969,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP21H02867"],"award-info":[{"award-number":["JP21H02867"]}]},{"name":"JSPS KAKENHI","award":["JP24K02394"],"award-info":[{"award-number":["JP24K02394"]}]},{"name":"The Mitani Foundation for Research and Development","award":["JP21H02867"],"award-info":[{"award-number":["JP21H02867"]}]},{"name":"The Mitani Foundation for Research and Development","award":["JP24K02394"],"award-info":[{"award-number":["JP24K02394"]}]},{"name":"Terumo life science foundation","award":["JP21H02867"],"award-info":[{"award-number":["JP21H02867"]}]},{"name":"Terumo life science foundation","award":["JP24K02394"],"award-info":[{"award-number":["JP24K02394"]}]},{"name":"Program of the Network-type Joint Usage\/Research Center for Radiation Disaster Medical Science","award":["JP21H02867"],"award-info":[{"award-number":["JP21H02867"]}]},{"name":"Program of the Network-type Joint Usage\/Research Center for Radiation Disaster Medical Science","award":["JP24K02394"],"award-info":[{"award-number":["JP24K02394"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The prostate-specific membrane antigen (PSMA) is a well-established target for radiotheranostics in prostate cancer. We previously demonstrated that 4-(p-astatophenyl)butyric acid (APBA), an albumin-binding moiety (ABM) labeled with astatine-211 (211At), enables the modulation of pharmacokinetics and enhancement of therapeutic efficacy when combined with the post-administration of an albumin-binding competitor. However, this strategy has not been explored in PSMA-targeting ligands. We designed and synthesized [211At]6, a novel PSMA ligand structurally analogous to PSMA-617 with APBA. The compound was obtained via a tin\u2013halogen exchange reaction from the corresponding tributylstannyl precursor. Comparative cellular uptake and biodistribution studies were conducted with [211At]6, its radioiodinated analog [125I]5, and [67Ga]Ga-PSMA-617. To assess pharmacokinetic modulation, sodium 4-(p-iodophenyl)butanoate (IPBA), an albumin-binding competitor, was administered 1 h postinjection of [125I]5 and [211At]6 at a 10-fold molar excess relative to blood albumin. The synthesis of [211At]6 gave a radiochemical yield of 15.9 \u00b1 7.7% and a radiochemical purity &gt; 97%. The synthesized [211At]6 exhibited time-dependent cellular uptake and internalization, with higher uptake levels than [67Ga]Ga-PSMA-617. Biodistribution studies of [211At]6 in normal mice revealed a prolonged blood retention similar to those of [125I]5. Notably, post-administration of IPBA significantly reduced blood radioactivity and non-target tissue accumulation of [125I]5 and [211At]6. We found that ABM-mediated pharmacokinetic control was applicable to PSMA-targeted radiotherapeutics, broadening its potential for the optimization of radiotheranostics.<\/jats:p>","DOI":"10.3390\/molecules30132804","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:37:51Z","timestamp":1751283471000},"page":"2804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Engineering a Radiohybrid PSMA Ligand with an Albumin-Binding Moiety and Pharmacokinetic Modulation via an Albumin-Binding Competitor for Radiotheranostics"],"prefix":"10.3390","volume":"30","author":[{"given":"Saki","family":"Hirata","sequence":"first","affiliation":[{"name":"Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Echigo","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3405-4512","authenticated-orcid":false,"given":"Masayuki","family":"Munekane","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5071-7574","authenticated-orcid":false,"given":"Kenji","family":"Mishiro","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9908-8756","authenticated-orcid":false,"given":"Kohshin","family":"Washiyama","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Fukushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-1212","authenticated-orcid":false,"given":"Takeshi","family":"Fuchigami","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University, Takara-machi 13-1, Kanazawa 920-8641, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7855-575X","authenticated-orcid":false,"given":"Kazuhiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Fukushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Kinuya","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University, Takara-machi 13-1, Kanazawa 920-8641, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1691-7302","authenticated-orcid":false,"given":"Kazuma","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","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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