{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:01:50Z","timestamp":1777694510166,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T00:00:00Z","timestamp":1720915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Introduction: The term theragnostic refers to the combination of a predictive imaging biomarker with a therapeutic agent. The promising application of prostate-specific membrane antigen (PSMA)-based radiopharmaceuticals in the imaging and treatment of prostate cancer (PCa) patients opens the way to investigate a possible role of PSMA-based radiopharmaceuticals in cancers beyond the prostate. Therefore, the aim of this review was to evaluate the role of 177Lu-PSMA radioligand therapy (RLT) in malignancies other than prostate cancer by evaluating preclinical, clinical studies, and ongoing clinical trials. Methods: An extensive literature search was performed in three different databases using different combinations of the following terms: \u201cLu-PSMA\u201d, \u201c177Lu-PSMA\u201d, \u201cpreclinical\u201d, \u201cmouse\u201d, \u201csalivary gland cancer\u201d, \u201cbreast cancer\u201d, \u201cglioblastoma\u201d, \u201csolid tumour\u201d, \u201crenal cell carcinoma\u201d, \u201cHCC\u201d, \u201cthyroid\u201d, \u201csalivary\u201d, \u201cradioligand therapy\u201d, and \u201clutetium-177\u201d. The search had no beginning date limit and was updated to April 2024. Only articles written in English were included in this review. Results: A total of four preclinical studies were selected (breast cancer model n = 3\/4). PSMA-RLT significantly reduced cell viability and had anti-angiogenic effects, especially under hypoxic conditions, which increase PSMA binding and uptake. Considering the clinical studies (n = 8), the complexity of evaluating PSMA-RLT in cancers other than prostate cancer was clearly revealed, since in most of the presented cases a sufficient tumour radiation dose was not achieved. However, encouraging results can be found in some types of diseases, such as thyroid cancer. Some clinical trials are still ongoing, and results from prospective larger cohorts of patients are awaited. Conclusions: The need for larger patient cohorts and more RLT cycles administered underscores the need for further comprehensive studies. Given the very preliminary results of both preclinical and clinical studies, ongoing clinical trials in the near future may provide stronger evidence of both the safety and therapeutic efficacy of PSMA-RLT in malignancies other than prostate cancer.<\/jats:p>","DOI":"10.3390\/bioengineering11070714","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T15:17:06Z","timestamp":1721056626000},"page":"714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prostate-Specific Membrane Antigen Radioligand Therapy in Non-Prostate Cancers: Where Do We Stand?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4839-9033","authenticated-orcid":false,"given":"Francesco","family":"Dondi","sequence":"first","affiliation":[{"name":"Nuclear Medicine Unit, ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Miceli","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Rovera","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Division, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-9472","authenticated-orcid":false,"given":"Vanessa","family":"Feudo","sequence":"additional","affiliation":[{"name":"Unit of Nuclear Medicine, Aosta Regional Hospital, 11100 Aosta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Battisti","sequence":"additional","affiliation":[{"name":"Section of Nuclear Medicine, Interdisciplinary Department of Medicine, University of Bari \u201cAldo Moro\u201d, Piazza Giulio Cesare 11, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1936-2848","authenticated-orcid":false,"given":"Maria","family":"Rondini","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Fondazione Istituto G. Giglio, 90015 Cefal\u00f9, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-3615","authenticated-orcid":false,"given":"Andrea","family":"Marongiu","sequence":"additional","affiliation":[{"name":"Unit of Nuclear Medicine, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Mura","sequence":"additional","affiliation":[{"name":"Unit of Nuclear Medicine, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0101-444X","authenticated-orcid":false,"given":"Riccardo","family":"Camedda","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-4838","authenticated-orcid":false,"given":"Maria Silvia","family":"De Feo","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Department of Radiological Sciences, Oncology and Anatomo-Pathology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1677-4858","authenticated-orcid":false,"given":"Miriam","family":"Conte","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Department of Radiological Sciences, Oncology and Anatomo-Pathology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Gorica","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Department of Radiological Sciences, Oncology and Anatomo-Pathology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0168-8551","authenticated-orcid":false,"given":"Cristina","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Section of Nuclear Medicine, Interdisciplinary Department of Medicine, University of Bari \u201cAldo Moro\u201d, Piazza Giulio Cesare 11, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9046-6378","authenticated-orcid":false,"given":"Anna Giulia","family":"Nappi","sequence":"additional","affiliation":[{"name":"Section of Nuclear Medicine, Interdisciplinary Department of Medicine, University of Bari \u201cAldo Moro\u201d, Piazza Giulio Cesare 11, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-0686","authenticated-orcid":false,"given":"Giulia","family":"Santo","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Department of Experimental and Clinical Medicine, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1S","DOI":"10.2967\/jnumed.117.199570","article-title":"Theranostic Concepts: More Than Just a Fashion Trend-Introduction and Overview","volume":"58","author":"Herrmann","year":"2017","journal-title":"J. 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