{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:34Z","timestamp":1787028574209,"version":"build-2736575974"},"reference-count":99,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>The growing use of experimental radiopharmaceuticals for targeted radionuclide therapy (TRT) highlights the need for robust \u201cin house\u201d radiolabeling protocols. Among these, PSMA-ALB-56 is a PSMA ligand incorporating an albumin-binding moiety to enhance pharmacokinetics, which showed promise for prostate cancer treatment. This study investigated manual radiolabeling conditions of this vector molecule with lutetium-177 and developed a corresponding automated synthesis protocol. Manual experiments on low activities explored buffer systems and antioxidants, identifying sodium acetate buffer and L-methionine as optimal, achieving radiochemical purities above 97% with excellent stability over 48 h. However, when these conditions were transposed directly to an automated process on a GAIA\u00ae module with activities &gt; 2 GBq, radiochemical purity dropped below 70% due to significant radiolysis. This result emphasized that conditions optimized at low activities are not directly transferable to high-activity automated production, and highlighted the crucial role of antioxidant concentration. An optimized automated method was subsequently developed, integrating a solid-phase extraction purification step, higher antioxidant levels during radiolabeling and formulation, and a larger final product volume. These changes led to radiochemical purities above 98.9% and excellent product stability over 120 h for 3 test batches. The presence of high concentrations of methionine and ascorbic acid was essential to protect against radiolysis. This work underscores the importance of adjusting radiolabeling strategies during process scale-up and confirmed that antioxidant concentration is essential for successful 177Lu radiolabeling. The optimized automated method developed here for [177Lu]Lu-PSMA-ALB-56 may also be adapted to other radiopharmaceuticals in development for TRT.<\/jats:p>","DOI":"10.3390\/ijms26199642","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T16:18:33Z","timestamp":1759421913000},"page":"9642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tailored Reaction Conditions and Automated Radiolabeling of [177Lu]Lu-PSMA-ALB-56 in a 68Ga Setting: The Critical Impact of Antioxidant Concentrations"],"prefix":"10.3390","volume":"26","author":[{"given":"Johanne","family":"Vanney","sequence":"first","affiliation":[{"name":"Nuclear Medicine Department, Institut R\u00e9gional du Cancer de Montpellier (ICM), University Montpellier, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Rubira","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Institut R\u00e9gional du Cancer de Montpellier (ICM), University Montpellier, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Torchio","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Institut R\u00e9gional du Cancer de Montpellier (ICM), University Montpellier, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4455-4641","authenticated-orcid":false,"given":"Cyril","family":"Fersing","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Institut R\u00e9gional du Cancer de Montpellier (ICM), University Montpellier, 34090 Montpellier, France"},{"name":"IBMM, University Montpellier, CNRS, ENSCM, 34293 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lepareur, N., Ram\u00e9e, B., Mougin-Degraef, M., and Bourgeois, M. 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