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This study investigates the direct relation between [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 uptake on PET and PSMA expression in the tumour micro-environment of high-grade glioma (HGG) and brain metastasis (BM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twelve patients with HGG (glioblastoma\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096, oligodendroglioma\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), or BM (lung-\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094, breast cancer\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), underwent PET-MRI after intravenous [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 injection (1.5\u00a0MBq\/kg), followed by image-guided biopsy sampling during (re-)resection surgery. Multiple samples (median\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093\/patient,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923 HGG\/\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920 BM) from locations of low and high [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 uptake were analysed for PSMA expression in vasculature and non-vascular structures using morphology and immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients showed [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 uptake in tumour ( SUVmax median, range: 10.5, 4.7\u201319.8). Strong PSMA expression was found in tumour microvasculature (14\/23, 61% in HGG, 13\/20, 65% in BM). Tumour cell PSMA expression was found in a subset of HGG (10\/23; of which strong in 8\/10) and BM (3\/20; none of which showed strong expression). Strong PSMA expression was also found on non-malignant glial cells in tumour. PSMA expression in healthy brain control samples was negligible. In HGG, a significant correlation existed between [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 uptake and PSMA expression in tumour microvasculature (r\u2009=\u20090.487,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01), but not tumour cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PSMA expression in brain tumours is predominately vascular, which likely explains why microvascular (rather than tumour cell) PSMA expression correlates with [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 uptake in HGG. This neovascular expression is crucial information for future PSMA-based RLT studies, as alpha-emitters may not sufficiently target tumour DNA.\n                    <\/jats:p>\n                    <jats:p>NCT05798273; date of registration: 1\/9\/2020.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07338-4","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T21:55:08Z","timestamp":1748210108000},"page":"4870-4881","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["PSMA radioligand uptake correlates with PSMA expression in high-grade glioma and brain metastasis: insights from a prospective PET-MRI guided multiregional biopsy study"],"prefix":"10.1007","volume":"52","author":[{"given":"Ilanah J.","family":"Pruis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"van Dis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sybren L. 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