{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:40:48Z","timestamp":1785260448622,"version":"3.55.0"},"reference-count":46,"publisher":"Georg Thieme Verlag KG","issue":"09","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rofo"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Theranostics in nuclear oncology combines diagnostic and therapeutic procedures using radiotracers to target tumor cells. Prostate-specific membrane antigen (PSMA) is a key target in metastatic prostate cancer, and the radioligand [177Lu]Lu-PSMA-617, which binds to PSMA, has shown promising results in treating metastatic castration-resistant prostate cancer (mCRPC), leading to its approval by the European Medicines Agency in 2022.<\/jats:p><jats:p>In this narrative review, the current evidence of [177Lu]Lu-PSMA-617 in mCRPC was discussed in the context of selected studies and the joint EANM\/SNMMI guidelines for Lutetium-177-labeled PSMA-targeted radioligand therapy.<\/jats:p><jats:p>The use of [177Lu]Lu-PSMA-617 for post-chemotherapy mCRPC is supported by substantial evidence from the phase II TheraP and the phase III VISION trials, demonstrating its safety and efficacy. The theranostic approach identifies patients likely to benefit from [177Lu]Lu-PSMA-617, which is effective only in tumors with sufficient PSMA expression, as detected by PSMA-ligand PET\/CT, which is also used for response assessment.<\/jats:p><jats:p>The success of [177Lu]Lu-PSMA-617 in post-chemotherapy mCRPC patients has led to further ongoing studies evaluating its use earlier in the treatment sequence, prior to chemotherapy. To ensure beneficial treatment outcome, adequate patient selection and evaluation of imaging-based response through PSMA-ligand PET\/CT is necessary.<\/jats:p>","DOI":"10.1055\/a-2514-4523","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T18:40:38Z","timestamp":1737571238000},"page":"1033-1042","source":"Crossref","is-referenced-by-count":2,"title":["Overview of selected completed prospective studies on PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer"],"prefix":"10.1055","volume":"197","author":[{"given":"Amir","family":"Karimzadeh","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencke","family":"Lehnert","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-9627","authenticated-orcid":false,"given":"Daniel","family":"Koehler","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzad","family":"Shenas","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kisters","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivayla","family":"Apostolova","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Klutmann","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4174-0959","authenticated-orcid":false,"given":"Markus","family":"Sauer","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref1","first-page":"81","article-title":"Prostate-specific membrane antigen expression in normal and malignant human tissues","volume":"3","author":"DA Silver","year":"1997","journal-title":"Clin Cancer Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/s0090-4295(98)00278-7","article-title":"Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases","volume":"52","author":"SD Sweat","year":"1998","journal-title":"Urology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.eururo.2019.06.030","article-title":"Prostate-specific Membrane Antigen Heterogeneity and DNA Repair Defects in Prostate Cancer","volume":"76","author":"A Paschalis","year":"2019","journal-title":"Eur Urol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"689","DOI":"10.3390\/biomedicines10030689","article-title":"Definition of Castrate Resistant Prostate Cancer: New Insights","volume":"10","author":"J Morote","year":"2022","journal-title":"Biomedicines"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"914","DOI":"10.2967\/jnumed.114.147413","article-title":"Preclinical Evaluation of a Tailor-Made DOTA-Conjugated PSMA Inhibitor with Optimized Linker Moiety for Imaging and Endoradiotherapy of Prostate Cancer","volume":"56","author":"M Bene\u0161ov\u00e1","year":"2015","journal-title":"J Nucl Med"},{"key":"ref6","first-page":"4055","article-title":"Constitutive and antibody-induced internalization of prostate-specific membrane antigen","volume":"58","author":"H Liu","year":"1998","journal-title":"Cancer Res"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s13550-015-0114-2","article-title":"Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study","volume":"5","author":"H Ahmadzadehfar","year":"2015","journal-title":"EJNMMI Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"12477","DOI":"10.18632\/oncotarget.7245","article-title":"Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer","volume":"7","author":"H Ahmadzadehfar","year":"2016","journal-title":"Oncotarget"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.2967\/jnumed.115.171397","article-title":"PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617","volume":"57","author":"C Kratochwil","year":"2016","journal-title":"J Nucl Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.2967\/jnumed.116.173757","article-title":"Response and Tolerability of a Single Dose of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: A Multicenter Retrospective Analysis","volume":"57","author":"K Rahbar","year":"2016","journal-title":"J Nucl Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1097\/RLU.0000000000001240","article-title":"Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer","volume":"41","author":"K Rahbar","year":"2016","journal-title":"Clin Nucl Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.2967\/jnumed.116.183194","article-title":"German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients","volume":"58","author":"K Rahbar","year":"2017","journal-title":"J Nucl Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/S1470-2045(18)30198-0","article-title":"177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial","volume":"19","author":"MS Hofman","year":"2018","journal-title":"Lancet Oncol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S0140-6736(21)00237-3","article-title":"177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP","volume":"397","author":"MS Hofman","year":"2021","journal-title":"Lancet"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"230","DOI":"10.4103\/0976-500X.119704","article-title":"Cabazitaxel: A novel taxane for metastatic castration-resistant prostate cancer-current implications and future prospects","volume":"4","author":"A Abidi","year":"2013","journal-title":"J Pharmacol Pharmacother"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"O Sartor","year":"2021","journal-title":"N Engl J Med"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2830","DOI":"10.1007\/s00259-023-06255-8","article-title":"Joint EANM\/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT)","volume":"50","author":"C Kratochwil","year":"2023","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S1470-2045(23)00529-6","article-title":"Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial","volume":"25","author":"MS Hofman","year":"2024","journal-title":"Lancet Oncol"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.085","article-title":"LBA13 Phase III trial of [177Lu]Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore)","author":"O Sartor","year":"2023","journal-title":"Annals of Oncology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.2967\/jnumed.122.265346","article-title":"The Impact of PSMA PET-Based Eligibility Criteria Used in the Prospective Phase II TheraP Trial in Metastatic Castration-Resistant Prostate Cancer Patients Undergoing Prostate-Specific Membrane Antigen-Targeted Radioligand Therapy","volume":"64","author":"A Karimzadeh","year":"2023","journal-title":"J Nucl Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.2967\/jnumed.121.263441","article-title":"Outcome of Patients with PSMA PET\/CT Screen Failure by VISION Criteria and Treated with 177Lu-PSMA Therapy: A Multicenter Retrospective Analysis","volume":"63","author":"M Hotta","year":"2022","journal-title":"J Nucl Med"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"731","DOI":"10.2967\/jnumed.122.264741","article-title":"Is 18F-FDG PET Needed to Assess 177Lu-PSMA Therapy Eligibility? A VISION-like, Single-Center Analysis","volume":"64","author":"R Seifert","year":"2023","journal-title":"J Nucl Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.2967\/jnumed.123.265952","article-title":"SNMMI Consensus Statement on Patient Selection and Appropriate Use of 177Lu-PSMA-617 Radionuclide Therapy","volume":"64","author":"TA Hope","year":"2023","journal-title":"J Nucl Med"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"7812","DOI":"10.7150\/thno.47251","article-title":"Analysis of PSMA expression and outcome in patients with advanced Prostate Cancer receiving 177Lu-PSMA-617 Radioligand Therapy","volume":"10","author":"R Seifert","year":"2020","journal-title":"Theranostics"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/S1470-2045(22)00605-2","article-title":"PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial","volume":"23","author":"JP Buteau","year":"2022","journal-title":"Lancet Oncol"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.5002","article-title":"[68Ga]Ga-PSMA-11 PET baseline imaging as a prognostic tool for clinical outcomes to [177Lu]Lu-PSMA-617 in patients with mCRPC: A VISION substudy","author":"P Kuo","year":"2022","journal-title":"JCO"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"517","DOI":"10.2967\/jnumed.118.219352","article-title":"Dosimetry of 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: Correlations Between Pretherapeutic Imaging and Whole-Body Tumor Dosimetry with Treatment Outcomes","volume":"60","author":"J Violet","year":"2019","journal-title":"J Nucl Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/S1470-2045(21)00274-6","article-title":"Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study","volume":"22","author":"A Gafita","year":"2021","journal-title":"Lancet Oncol"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1726862","article-title":"PSMA- and FDG-PET mismatch assessment for optimized selection of PSMA radioligand therapy candidates","author":"P Sandach","year":"2021","journal-title":"Nuklearmedizin"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1007\/s00259-020-05160-8","article-title":"Prognostic implications of dual tracer PET\/CT: PSMA ligand and [18F]FDG PET\/CT in patients undergoing [177Lu]PSMA radioligand therapy","volume":"48","author":"K Michalski","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1055\/a-2088-9543","article-title":"PSMA hybrid imaging in prostate cancer \u2013 current applications and perspectives. PSMA-Hybridbildgebung in der Diagnostik des Prostatakarzinoms \u2013 aktuelle Anwendungen und Perspektiven","volume":"195","author":"D Koehler","year":"2023","journal-title":"Fortschr R\u00f6ntgenstr"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40644-019-0211-y","article-title":"Intra-individual comparison of 68Ga-PSMA-11 and 18F-DCFPyL normal-organ biodistribution","volume":"19","author":"G Ferreira","year":"2019","journal-title":"Cancer Imaging"},{"issue":"02","key":"ref34","doi-asserted-by":"publisher","first-page":"221","DOI":"10.2967\/jnumed.122.264398","article-title":"Evaluation of 177Lu-PSMA-617 SPECT\/CT Quantitation as a Response Biomarker Within a Prospective 177Lu-PSMA-617 and NOX66 Combination Trial (LuPIN)","volume":"64","author":"S Pathmanandavel","year":"2023","journal-title":"J Nucl Med"},{"issue":"05","key":"ref35","doi-asserted-by":"publisher","first-page":"689","DOI":"10.2967\/jnumed.119.231431","article-title":"Response Prediction of 177Lu-PSMA-617 Radioligand Therapy Using Prostate-Specific Antigen, Chromogranin A, and Lactate Dehydrogenase","volume":"61","author":"H Rathke","year":"2020","journal-title":"J Nucl Med"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1055\/s-00034924","article-title":"99mTc-MIP-1404 SPECT\/CT for baseline staging and assessment of eligibility for subsequent 177Lu-PSMA RLT: first clinical experience","author":"T Derlin","year":"2024","journal-title":"Nuklearmedizin"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1200\/JCO.2015.64.2702","article-title":"Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3","volume":"34","author":"HI Scher","year":"2016","journal-title":"J Clin Oncol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.2967\/jnumed.121.263072","article-title":"Novel Framework for Treatment Response Evaluation Using PSMA PET\/CT in Patients with Metastatic Castration-Resistant Prostate Cancer (RECIP 1.0): An International Multicenter Study [published correction appears in J Nucl Med. 2023 Sep;64(9):1503]","volume":"63","author":"A Gafita","year":"2022","journal-title":"J Nucl Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.1007\/s00259-022-05882-x","article-title":"Measuring response in metastatic castration-resistant prostate cancer using PSMA PET\/CT: comparison of RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 criteria","volume":"49","author":"A Gafita","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"79","DOI":"10.2967\/jnumed.123.265986","article-title":"Long-Term Nephrotoxicity of 177Lu-PSMA Radioligand Therapy","volume":"65","author":"L Steinhelfer","year":"2024","journal-title":"J Nucl Med"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00259-021-05345-9","article-title":"EANM position paper on article 56 of the Council Directive 2013\/59\/Euratom (basic safety standards) for nuclear medicine therapy","volume":"48","author":"M Konijnenberg","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1055\/s-0037-1616480","article-title":"Therapie mit 177Lu-PSMA-617, Dosimetrie und Nachsorge beim metastasierten kastrationsresistenten Prostatakarzinom","volume":"55","author":"WP Fendler","year":"2016","journal-title":"Nuklearmedizin"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"71","DOI":"10.2967\/jnumed.123.265448","article-title":"Renal and Multiorgan Safety of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer in the VISION Dosimetry Substudy","volume":"65","author":"K Herrmann","year":"2024","journal-title":"J Nucl Med"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1097\/MNM.0000000000001535","article-title":"Dosimetry in Lu-177-PSMA-617 prostate-specific membrane antigen targeted radioligand therapy: a systematic review","volume":"43","author":"A Nautiyal","year":"2022","journal-title":"Nuclear Medicine Communications"},{"key":"ref48","first-page":"37","article-title":"MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates","volume":"40","author":"JA Siegel","year":"1999","journal-title":"J Nucl Med"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"3884","DOI":"10.3390\/cancers13153884","article-title":"Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer","volume":"13","author":"J Kurth","year":"2021","journal-title":"Cancers (Basel)"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"767","DOI":"10.2967\/jnumed.122.264594","article-title":"Toward Single-Time-Point Image-Based Dosimetry of 177Lu-PSMA-617 Therapy","volume":"64","author":"J Brosch-Lenz","year":"2023","journal-title":"J Nucl Med"}],"container-title":["R\u00f6Fo - Fortschritte auf dem Gebiet der R\u00f6ntgenstrahlen und der bildgebenden Verfahren"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2514-4523.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T22:39:41Z","timestamp":1755643181000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2514-4523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":46,"journal-issue":{"issue":"09","published-online":{"date-parts":[[2025,8,19]]},"published-print":{"date-parts":[[2025,9]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2514-4523","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["1438-9029","1438-9010"],"issn-type":[{"value":"1438-9029","type":"print"},{"value":"1438-9010","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,22]]}}}