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Radiation might improve response to immunotherapy by increasing the immunogenicity of prostate cancer. The objective of this study was to investigate radium-223-mediated changes in the micro- and macroenvironment of mCRPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective, multicenter study (ICTRP NL-OMON26890), 28 patients with mCRPC and predominantly bone metastases were treated with radium-223, according to standard-of-care. Primary endpoint was failure-free survival (FFS). Imaging included sequential positron emission tomography (PET) with gallium-68 prostate-specific membrane antigen (\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA) and zirconium-89 atezolizumab (\n                      <jats:sup>89<\/jats:sup>\n                      Zr-atezolizumab) to quantify whole-body expression of PD-L1 in vivo (SUV\n                      <jats:sub>mean\/max<\/jats:sub>\n                      ). Paired PET analysis included nine patients. The immune status of patients was characterized in biopsies from bone metastases and in blood using (multiplex) immunohistochemistry (IHC) and flow cytometry, respectively. Sequential biopsy analysis included two patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:sup>89<\/jats:sup>\n                      Zr-atezolizumab uptake in\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA positive bone metastases showed high intra- and inter-patient heterogeneity. In the total volume of\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA-positive bone lesions, the median SUV\n                      <jats:sub>mean<\/jats:sub>\n                      of\n                      <jats:sup>89<\/jats:sup>\n                      Zr-atezolizumab was 2.5 (IQR 0.9\u20133.4) at baseline and 0.9 (IQR 0.5\u20132.5) after three cycles of radium-223, which was higher than the physiological uptake in bone marrow at baseline and after treatment with radium-223. After three cycles of radium-223,\n                      <jats:sup>89<\/jats:sup>\n                      Zr-atezolizumab uptake decreased in bone metastases, independent of response on\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA PET, and the number of lymphocytes in tumor tissue and blood decreased concomitantly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment of mCRPC bone metastases with radium-223 results in a significant decrease of in vivo PD-L1-expression on PET imaging and a decrease in immune cells in bone metastases and blood. These findings indicate that treatment with alpha emitting radium-223 alters the immune microenvironment, thereby potentially reducing the efficacy of PD-(L)1 inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08175-9","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:41:47Z","timestamp":1789173707000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radium-223 decreases PD-L1 expression in bone metastases: A study with [89Zr]Zr-atezolizumab PET and immunohistological correlation"],"prefix":"10.1007","author":[{"given":"Sui Wai","family":"Ling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gorris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Segbers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Graven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"van Driel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"van Leenders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khrystany","family":"Isebia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolijn Lub \u2013","family":"de Hooge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Hamberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niven","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"van Brakel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"de Wit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reno","family":"Debets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Brabander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanda","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"van der Veldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"issue":"3","key":"8175_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. 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All patients gave written informed consent before any study procedure.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients gave written informed consent for publication.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"PH reports consulting fees for Astellas, MSD, Pfizer AstraZeneca, BMS, Ipsen and Bayer. RdW reports advisory fees for Bayer, Astellas, Merck, Seagen, speaker fees and grant support (paid to institution) for Bayer. NM has received consultancy fees from Astellas; research support from Astellas, Janssen, AstraZeneca\/MSD, Pfizer, BMS, and Roche; and honoraria from AstraZeneca\/MSD, Pfizer, BMS, Janssen, Astellas. EdV reports institutional financial support for advisory boards\/consultancy from NSABP, Daiichi Sankyo, and Crescendo Biologics and institutional financial support for clinical trials or contracted research grants from Amgen, Genentech, Roche, Bayer, Servier, Regeneron, and Crescendo Biologics; outside the submitted work. AvdV reports advisory fees (all paid to the institution) from BMS, Eisai, Ipsen, MSD, Sanofi, Novartis, Pfizer, Pierre Fabre, Roche and travel fees from Ipsen; outside the submitted work. All other authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}