{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:37:04Z","timestamp":1792143424250,"version":"4.4.0"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Purpose: PSMA-targeted radioligand therapy (PRLT) is a promising treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, a high uptake of the radiopharmaceutical in the salivary glands (SG) can lead to xerostomia and becomes dose-limiting for 225Ac-PSMA-617. This study investigated the sialotoxicity of 177Lu-PSMA-I&amp;T\/-617 monotherapy and co-administered 225Ac-PSMA-617 and 177Lu-PSMA-617 (Tandem-PPRLT). Methods: Three patient cohorts, that had undergone 177Lu-PSMA-I&amp;T\/-617 monotherapy or Tandem-PRLT, were retrospectively analyzed. In a short-term cohort (91 patients), a xerostomia assessment (CTCAE v.5.0), a standardized questionnaire (sXI), salivary gland scintigraphy (SGS), and SG SUVmax and the metabolic volume (MV) on 68Ga-PSMA-11-PET\/CT were obtained before and after two cycles of 177Lu-PSMA-I&amp;T\/-617. In a long-term cohort, 40 patients were similarly examined. In a Tandem cohort, the same protocol was applied to 18 patients after one cycle of Tandem-PRLT. Results: Grade 1 xerostomia in the short-term follow-up was observed in 22 (24.2%) patients with a worsening of sXI from 7 to 8 at (p &lt; 0.05). In the long-term cohort, xerostomia grades 1 to 2 occurred in 16 (40%) patients. SGS showed no significant changes, but there was a decline of the MV of all SGs. After Tandem-PRLT, 12\/18 (66.7%) patients reported xerostomia grades 1 to 2, and the sXI significantly worsened from 9.5 to 14.0 (p = 0.005), with a significant reduction in the excretion fraction (EF) and MV of all SGs. Conclusion: 177Lu-PSMA-I&amp;T\/-617 causes only minor SG toxicity, while one cycle of Tandem-PRLT results in a significant SG impairment. This standardized protocol may help to objectify and quantify SG dysfunction.<\/jats:p>","DOI":"10.3390\/diagnostics12081926","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T04:20:32Z","timestamp":1660105232000},"page":"1926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Salivary Gland Toxicity of PSMA-Targeted Radioligand Therapy with 177Lu-PSMA and Combined 225Ac- and 177Lu-Labeled PSMA Ligands (TANDEM-PRLT) in Advanced Prostate Cancer: A Single-Center Systematic Investigation"],"prefix":"10.3390","volume":"12","author":[{"given":"Thomas","family":"Langbein","sequence":"first","affiliation":[{"name":"Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, 99438 Bad Berka, Germany"},{"name":"Department of Nuclear Medicine, Technical University of Munich, Klinikum Rechts der Isar, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshad R.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, 99438 Bad Berka, Germany"},{"name":"BAMF Health, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Schuchardt","sequence":"additional","affiliation":[{"name":"Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, 99438 Bad Berka, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Mueller","sequence":"additional","affiliation":[{"name":"Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, 99438 Bad Berka, Germany"},{"name":"Department of Nuclear Medicine, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1245-6331","authenticated-orcid":false,"given":"Gerd Fabian","family":"Volk","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Facial-Nerve-Center Jena, Center for Rare Diseases Jena, Jena University Hospital, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-0075","authenticated-orcid":false,"given":"Richard P.","family":"Baum","sequence":"additional","affiliation":[{"name":"Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, 99438 Bad Berka, Germany"},{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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