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Radioligand therapies are approved in extracranial malignancies, but their value in brain tumours including meningiomas is unclear, as data on target expression is scarce.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>CNS WHO grade 2 and 3 meningioma samples were immunohistochemically stained for somatostatin receptor 2a (SSTR2a), fibroblast activation protein (FAP), and human epidermal growth factor receptors 2\/3 (HER2\/HER3). Target expression was correlated with (epi-)genetic tumour subtyping by DNA methylation analysis, genetic alterations, and survival.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Meningioma samples of 58 patients were included. SSTR2a expression (membranous\/cytoplasmic) was observed in 43\/55 (78.2%), and FAP expression in 15\/58 (25.9%) evaluable samples, with HER2 and HER3 expression in one specimen each (1.7%). Membranous SSTR2a expression was strong in 18 (32.7%), intermediate in 12 (21.8%), and weak in 11 (20.0%) samples. While SSTR2a expression was more homogenous and mainly seen in regions with higher cellularity, FAP immunoreactivity was predominantly seen in tumour stroma and regions of lower cellularity. SSTR2a immunoreactivity was associated with <jats:italic>TRAF7<\/jats:italic> wildtype status (<jats:italic>p<\/jats:italic>\u2009=\u20090.034). FAP expression was more frequent in meningiomas of CNS WHO grade 3 (vs. CNS WHO 2; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and samples with <jats:italic>NF2<\/jats:italic> mutations (<jats:italic>p<\/jats:italic>\u2009=\u20090.032) or <jats:italic>CDKN2A\/B<\/jats:italic> deletions (<jats:italic>p<\/jats:italic>\u2009=\u20090.013) compared to wildtype. FAP and SSTR2a expression (present vs. absent) were not associated with overall survival (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>SSTR2a and FAP are expressed in high-grade meningioma samples to a variable extent, and differences across meningioma subtypes underscore the need for biomarkers to improve patient selection. Spatial heterogeneity of target expression should be considered in radioligand therapy design.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00259-025-07075-8","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:15:19Z","timestamp":1739942119000},"page":"2771-2781","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expression of SSTR2a, FAP, HER2 and HER3 as potential radionuclide therapy targets in higher-grade meningioma"],"prefix":"10.1007","volume":"52","author":[{"given":"Maximilian J.","family":"Mair","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Hartenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Tomasich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sybren L. 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Due to the retrospective nature of the study, no written informed consent was obtained in line with institutional regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Maximilian J. Mair has received research funding from Bristol-Myers Squibb and travel support from Pierre Fabre. Georg Widhalm has received honoraria for advisory board participation from Servier. Franziska Eckert has received travel grants and honoraria for lectures or advisory board from Dr. Sennewald Medizintechnik and Servier. Felix Sahm is co-founder and shareholder of Heidelberg Epignostix GmbH. Anna Sophie Berghoff has research support from Daiichi Sankyo, Roche and honoraria for lectures, consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo, AstraZeneca, CeCaVa, Seagen, Alexion, Servier as well as travel support from Roche, Amgen and AbbVie.Matthias Preusser has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, B\u00f6hringer-Ingelheim, Telix, Medscape. Nathalie L. Albert has received honoraria for lectures, consultation or advisory board participation from Novartis, Advanced Accelerator Applications, Servier, OncLive, Medsir and Telix Pharmaceuticals, and research funding from Novocure and Telix Pharmaceuticals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}