{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:13:56Z","timestamp":1782188036537,"version":"3.54.5"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1145","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:p>Bone and soft tissue sarcomas are a group of rare malignant tumours with major histological and anatomical varieties. In a metastatic setting, sarcomas have a poor prognosis due to limited response rates to chemotherapy. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may offer a new perspective. PSMA is a type II transmembrane glycoprotein which is present in all prostatic tissue and overexpressed in prostate cancer. Despite the name, PSMA is not prostate-specific. PSMA expression is also found in a multitude of non-prostatic diseases including a subgroup of sarcomas, mostly in its neovascular endothelial cells. On PET\/CT imaging, multiple sarcomas have also shown intense PSMA-tracer accumulation. PSMA expression and PSMA-tracer uptake seem to be highest in patients with aggressive and advanced sarcomas, who are also in highest need of new therapeutic options. Although these results provide a good rationale for the future use of PSMA-targeted radioligand therapy in a selection of sarcoma patients, more research is needed to gain insight into optimal patient selection methods, PSMA-targeting antibodies and tracers, administered doses of radioligand therapy, and their efficacy and tolerability. In this review, mRNA expression of the FOLH1 gene which encodes PSMA, PSMA immunohistochemistry, PSMA-targeted imaging and PSMA-targeted therapy in sarcomas will be discussed.<\/jats:p>","DOI":"10.1259\/bjr.20220886","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T15:16:05Z","timestamp":1675350965000},"source":"Crossref","is-referenced-by-count":15,"title":["Prostate-specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas"],"prefix":"10.1093","volume":"96","author":[{"given":"Fleur","family":"Kleiburg","sequence":"first","affiliation":[{"name":"Biomedical Photonic Imaging Group, University of Twente , Enschede, The Netherlands"},{"name":"Department of Radiology, section of Nuclear Medicine, Leiden University Medical Center , Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Heijmen","sequence":"additional","affiliation":[{"name":"Department of Radiology, section of Nuclear Medicine, Leiden University Medical Center , Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Gelderblom","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Leiden University Medical Center , Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon M","family":"Kielbasa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center , Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith VMG","family":"Bov\u00e9e","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center , Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lioe-Fee","family":"De Geus-Oei","sequence":"additional","affiliation":[{"name":"Biomedical Photonic Imaging Group, University of Twente , Enschede, The Netherlands"},{"name":"Department of Radiology, section of Nuclear Medicine, Leiden University Medical Center , Leiden, The Netherlands"},{"name":"Department of Radiation Science and Technology, Technical University of Delft , Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"2024050709590160900_b1","volume-title":"WHO Classification of tumours of soft tissue and bone","author":"WHO Classification of Tumours Editorial Board","year":"2020","edition":"5th edn"},{"key":"2024050709590160900_b2","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.ejca.2012.09.011","article-title":"Descriptive epidemiology of sarcomas in europe: report from the RARECARE project","volume":"49","author":"Stiller","year":"2013","journal-title":"Eur J Cancer"},{"key":"2024050709590160900_b3","unstructured":"National Cancer Institute\n          . SEER Cancer Stat Facts: Soft Tissue Cancer. Bethesda, MD. Available from: https:\/\/seer.cancer.gov\/statfacts\/html\/soft.html"},{"key":"2024050709590160900_b4","unstructured":"SEER Cancer Stat Facts: Bone and Joint Cancer. National Cancer Institute. Bethesda, MD [Available from: https:\/\/seer.cancer.gov\/statfacts\/html\/bones.html."},{"key":"2024050709590160900_b5","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/j.annonc.2021.07.006","article-title":"Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS clinical practice guidelines for diagnosis, treatment and follow-up\u2606","volume":"32","author":"Gronchi","year":"2021","journal-title":"Ann Oncol"},{"key":"2024050709590160900_b6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.annonc.2021.08.1995","article-title":"Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN paedcan clinical practice guideline for diagnosis, treatment and follow-up","volume":"32","author":"Strauss","year":"2021","journal-title":"Ann Oncol"},{"key":"2024050709590160900_b7","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1007\/s11999-013-3076-6","article-title":"How long should we follow patients with soft tissue sarcomas?","volume":"472","author":"Sawamura","year":"2014","journal-title":"Clin Orthop Relat Res"},{"issue":"1","key":"2024050709590160900_b8","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12010047","article-title":"Individualizing follow-up strategies in high-grade soft tissue sarcoma with flexible parametric competing risk regression models","volume":"12","author":"Smolle","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2024050709590160900_b9","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1038\/bjc.2014.200","article-title":"What is the role of routine follow-up for localised limb soft tissue sarcomas? A retrospective analysis of 174 patients","volume":"110","author":"Rothermundt","year":"2014","journal-title":"Br J Cancer"},{"key":"2024050709590160900_b10","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ejca.2018.11.027","article-title":"Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (european and american osteosarcoma study) cohort","volume":"109","author":"Smeland","year":"2019","journal-title":"Eur J Cancer"},{"key":"2024050709590160900_b11","volume-title":"Cancer Facts & Figures 2017","author":"American Cancer Society","year":"2017"},{"key":"2024050709590160900_b12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1200\/JCO.1999.17.1.150","article-title":"Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens -- a European organization for research and treatment of cancer soft tissue and bone sarcoma group study","volume":"17","author":"Van Glabbeke","year":"1999","journal-title":"J Clin Oncol"},{"key":"2024050709590160900_b13","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ejca.2009.09.022","article-title":"Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European organization for research and treatment of Cancer-Soft tissue and bone sarcoma group (EORTC-STBSG)","volume":"46","author":"Sleijfer","year":"2010","journal-title":"Eur J Cancer"},{"key":"2024050709590160900_b14","unstructured":"Cancer Statistics Explorer Network SEER*Explorer. National Cancer Institute. Available from. Available from: https:\/\/seer.cancer.gov\/statistics-network\/explorer\/application.html"},{"key":"2024050709590160900_b15","first-page":"S13","article-title":"Overview of prostate-specific membrane antigen","volume":"6","author":"Chang","year":"2004","journal-title":"Rev Urol"},{"key":"2024050709590160900_b16","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.630589","article-title":"Prostate-specific membrane antigen uptake and survival in metastatic castration-resistant prostate cancer","volume":"11","author":"Vlachostergios","year":"2021","journal-title":"Front Oncol"},{"key":"2024050709590160900_b17","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1084\/jem.20171052","article-title":"Prostate-Specific membrane antigen cleavage of vitamin B9 stimulates oncogenic signaling through metabotropic glutamate receptors","volume":"215","author":"Kaittanis","year":"2018","journal-title":"J Exp Med"},{"key":"2024050709590160900_b18","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1158\/1078-0432.CCR-08-1402","article-title":"Nuclear versus cytoplasmic localization of filamin A in prostate cancer: immunohistochemical correlation with metastases","volume":"15","author":"Bedolla","year":"2009","journal-title":"Clin Cancer Res"},{"key":"2024050709590160900_b19","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s00259-020-04934-4","article-title":"Consensus statements on PSMA PET\/CT response assessment criteria in prostate cancer","volume":"48","author":"Fanti","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2024050709590160900_b20","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N Engl J Med"},{"key":"2024050709590160900_b21","doi-asserted-by":"crossref","first-page":"62","DOI":"10.2967\/jnumed.119.229229","article-title":"Predictors of overall and disease-free survival in metastatic castration-resistant prostate cancer patients receiving 225ac-PSMA-617 radioligand therapy","volume":"61","author":"Sathekge","year":"2020","journal-title":"J Nucl Med"},{"issue":"1","key":"2024050709590160900_b22","doi-asserted-by":"crossref","DOI":"10.1186\/s40644-020-00300-7","article-title":"Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings","volume":"20","author":"de Galiza Barbosa","year":"2020","journal-title":"Cancer Imaging"},{"key":"2024050709590160900_b23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0167-4781(98)00200-0","article-title":"Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene","volume":"1443","author":"O\u2019Keefe","year":"1998","journal-title":"Biochim Biophys Acta"},{"key":"2024050709590160900_b24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cbio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"2024050709590160900_b25","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cbioportal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci Signal"},{"key":"2024050709590160900_b26","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2024050709590160900_b27","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.18632\/oncotarget.13994","article-title":"Expression of PSMA in tumor neovasculature of high grade sarcomas including synovial sarcoma, rhabdomyosarcoma, undifferentiated sarcoma and MPNST","volume":"8","author":"Heitk\u00f6tter","year":"2017","journal-title":"Oncotarget"},{"key":"2024050709590160900_b28","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1007\/s12032-011-0089-4","article-title":"Prostate-Specific membrane antigen: a new potential prognostic marker of osteosarcoma","volume":"29","author":"Zeng","year":"2012","journal-title":"Med Oncol"},{"key":"2024050709590160900_b29","first-page":"3192","article-title":"Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature","volume":"59","author":"Chang","year":"1999","journal-title":"Cancer Res"},{"key":"2024050709590160900_b30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1615\/JEnvironPatholToxicolOncol.2021039719","article-title":"Stat3, VEGF, and PSMA expression patterns in malignant peripheral nerve sheath tumors, malignant melanomas, and glioblastomas: does staining percentage and intensity have an effect on survival?","volume":"41","author":"Coskun","year":"2022","journal-title":"J Environ Pathol Toxicol Oncol"},{"key":"2024050709590160900_b31","doi-asserted-by":"crossref","first-page":"e334","DOI":"10.1097\/RLU.0000000000002189","article-title":"Incidental detection of tracer avidity in liposarcoma on 68ga-labeled prostate-specific membrane antigen PET\/CT","volume":"43","author":"Malik","year":"2018","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b32","doi-asserted-by":"crossref","first-page":"e612","DOI":"10.1097\/RLU.0000000000002762","article-title":"68Ga-PSMA PET\/CT in giant retroperitoneal liposarcoma","volume":"44","author":"Inanir","year":"2019","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b33","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1097\/RLU.0000000000002389","article-title":"68Ga-prostate-specific membrane antigen PET\/CT: incidental finding of a liposarcoma","volume":"44","author":"Militano","year":"2019","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b34","doi-asserted-by":"crossref","first-page":"e501","DOI":"10.1097\/RLU.0000000000002592","article-title":"Incidental detection of a radiation-induced soft-tissue sarcoma on 68ga-PSMA PET\/CT in a patient previously treated for prostate cancer","volume":"44","author":"Plouznikoff","year":"2019","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b35","doi-asserted-by":"crossref","first-page":"e120","DOI":"10.1097\/RLU.0000000000002760","article-title":"Incidental detection of pleomorphic sarcoma on 68ga-PSMA PET\/CT in a patient with prostate cancer","volume":"45","author":"Mathew","year":"2020","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b36","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1097\/RLU.0000000000002764","article-title":"68Ga-PSMA-HBED-CC PET\/CT and 18F-FDG PET\/CT in Ewing sarcoma","volume":"45","author":"Parihar","year":"2020","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b37","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1097\/RLU.0000000000001646","article-title":"68Ga-PSMA PET\/CT in osteosarcoma in fibrous dysplasia","volume":"42","author":"Sasikumar","year":"2017","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b38","doi-asserted-by":"crossref","first-page":"e233","DOI":"10.1097\/RLU.0000000000003320","article-title":"Is 68ga-prostate-specific membrane antigen PET\/CT superior than 18F-FDG PET\/CT for evaluation of metastatic osteosarcoma?","volume":"46","author":"Can","year":"2021","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b39","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1097\/RLU.0000000000003780","article-title":"Prostate-Specific membrane antigen expression in metastatic angiosarcoma detected on 18F-PMSA PET\/CT: a new potential prognostic marker","volume":"47","author":"Marafi","year":"2022","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b40","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1055\/a-0914-2486","article-title":"Experimental 177lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma","volume":"58","author":"J\u00fcptner","year":"2019","journal-title":"Nuklearmedizin"},{"key":"2024050709590160900_b41","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1136\/jitc-2022-005383","article-title":"First on the efficacy of combined177lutetium-PSMA with immunotherapy outside prostatecancer","volume":"10","author":"Digklia","year":"2022","journal-title":"J Immunother Cancer"},{"key":"2024050709590160900_b42","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/RLU.0000000000002428","article-title":"Splenic hemangioma as a potential pitfall on PSMA-targeted 18F-dcfpyl PET\/CT","volume":"44","author":"Chauss\u00e9","year":"2019","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b43","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1097\/RLU.0000000000001384","article-title":"Prostate-Specific membrane antigen PET\/CT findings for hepatic hemangioma","volume":"41","author":"Bhardwaj","year":"2016","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b44","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1097\/RLU.0000000000001542","article-title":"Subcutaneous lobular capillary hemangioma on 68ga-PSMA PET\/CT","volume":"42","author":"Jochumsen","year":"2017","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b45","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/RLU.0000000000001281","article-title":"Schwannoma showing avid uptake on 68ga-PSMA-HBED-CC PET\/CT","volume":"41","author":"Kanthan","year":"2016","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b46","article-title":"Schwannoma: a rare cause of false-positive 68ga-PSMA PET\/CT uptake in the evaluation of metastatic prostate cancer","volume":"41","author":"Gualberto","year":"2022","journal-title":"Urol Case Rep"},{"key":"2024050709590160900_b47","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1007\/s00259-021-05501-1","article-title":"What\u2019s behind 68ga-PSMA-11 uptake in primary prostate cancer PET? investigation of histopathological parameters and immunohistochemical PSMA expression patterns","volume":"48","author":"R\u00fcschoff","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2024050709590160900_b48","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1007\/s00259-019-04485-3","article-title":"EANM procedure guidelines for radionuclide therapy with 177lu-labelled PSMA-ligands (177lu-PSMA-RLT)","volume":"46","author":"Kratochwil","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2024050709590160900_b49","first-page":"7","article-title":"Healthy tissue uptake of (68)ga-prostate-specific membrane antigen, (18)F-dcfpyl, (18)F-fluoromethylcholine, and (18)F-dihydrotestosterone","volume":"60","author":"Jansen","year":"2019","journal-title":"J Nucl Med Mol Imaging"},{"key":"2024050709590160900_b50","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1007\/s00259-020-04715-z","article-title":"Tumor uptake in glioblastoma multiforme after IV injection of [ 177lu ] lu-psma-617","volume":"47","author":"Kunikowska","year":"2020","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2024050709590160900_b51","doi-asserted-by":"crossref","first-page":"e512","DOI":"10.1097\/RLU.0000000000003142","article-title":"177Lu-\/68ga-PSMA theranostics in recurrent glioblastoma multiforme: proof of concept","volume":"45","author":"Kumar","year":"2020","journal-title":"Clin Nucl Med"},{"key":"2024050709590160900_b52","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1007\/s00259-021-05661-0","article-title":"89zr-labeled PSMA ligands for pharmacokinetic PET imaging and dosimetry of PSMA-617 and PSMA-I & T: a preclinical evaluation and first in man","volume":"49","author":"Priv\u00e9","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2024050709590160900_b53","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/RLU.0000000000004108","article-title":"89Zr-PSMA-617 PET\/CT may reveal local recurrence of prostate cancer unidentified by 68ga-PSMA-11 PET\/CT","volume":"47","author":"Rosar","year":"2022","journal-title":"Clin Nucl Med"}],"container-title":["The British Journal of Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjr\/article-pdf\/96\/1145\/20220886\/57432580\/bjr.20220886.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjr\/article-pdf\/96\/1145\/20220886\/57432580\/bjr.20220886.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T10:01:00Z","timestamp":1715076060000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjr\/article\/doi\/10.1259\/bjr.20220886\/7469101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,3]]},"references-count":53,"journal-issue":{"issue":"1145","published-online":{"date-parts":[[2023,3,3]]},"published-print":{"date-parts":[[2023,5,1]]}},"URL":"https:\/\/doi.org\/10.1259\/bjr.20220886","relation":{},"ISSN":["0007-1285","1748-880X"],"issn-type":[{"value":"0007-1285","type":"print"},{"value":"1748-880X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,5,1]]},"published":{"date-parts":[[2023,3,3]]},"article-number":"20220886"}}