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[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs were conjugated to anti-epidermal growth factor receptor (EGFR) panitumumab or were non-targeted. Our aim was to compare the cytotoxicity and DNA-damaging properties in vitro of panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs and non-targeted [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs on U251-Luc human GBM cells and estimate their cellular dosimetry. We further aimed to compare the biodistribution in vivo of panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs and [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs after convection-enhanced delivery (CED) in NRG mice with U251-Luc tumours in the brain and estimate the absorbed doses in the tumour and surrounding margins of healthy brain.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs (26.8\u2009\u00b1\u20096.4\u00a0nm) were produced with a radiochemical yield of 98\u2009\u00b1\u20091% by incorporating <jats:sup>197<\/jats:sup>Hg into the Turkevich synthesis method, forming a mercury-gold amalgam. Panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs exhibited high affinity (K<jats:sub>D<\/jats:sub>\u2009=\u20091.8\u2009\u00d7\u200910<jats:sup>\u20139<\/jats:sup>\u00a0mol\/L) binding to EGFR-positive U251-Luc cells. The binding of panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs to U251-Luc cells was 15-fold higher than [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs, and internalization and nuclear uptake were 12-fold and 18-fold greater, respectively. Panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs caused 84-fold more DNA double-strand breaks (DSBs) in U251-Luc cells than [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs. Panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs were ninefold more effective at reducing the clonogenic survival of U251-Luc cells than [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs. Panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs were twofold more cytotoxic than non-radioactive panitumumab-AuNPs (<jats:italic>P<\/jats:italic>\u2009=\u20090.04) and fivefold more cytotoxic than panitumumab (<jats:italic>P<\/jats:italic>\u2009=\u20090.01). The absorbed doses in the nucleus of U251-Luc cells treated in vitro with panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs or [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs were 8.8\u2009\u00b1\u20092.9 Gy and 0.6\u2009\u00b1\u20090.1 Gy, respectively. SPECT\/CT imaging showed that panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs and [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs were strongly retained at the infusion site in the brain after CED up to 7 d in NRG mice with orthotopic U251-Luc tumours. Uptake of panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs in the tumour-bearing right hemisphere [484.5% injected dose\/g (%ID\/g)] was 172-fold and 579-fold greater than in the healthy left hemisphere and cerebellum, respectively. The uptake of [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs (423.9% ID\/g) in the tumour-bearing right hemisphere was 85-fold and 64-fold higher than the left hemisphere and cerebellum, respectively. Most normal tissue uptake was\u2009&lt;\u20091% ID\/g, except for kidneys (9\u201320% ID\/g), spleen (3.5\u20136.6% ID\/g) and liver (0.6\u20133.3% ID\/g). Dosimetry showed that 58% of the tumour received\u2009&gt;\u2009190 Gy for CED of 1.0 MBq of panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs vs. 0.6% of the tumour for non-targeted [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs, but both agents deposited\u2009&gt;\u200950 Gy in 95% of the tumour. Doses decreased dramatically to 1.7 and 3.3 Gy at 1\u20133 mm from the tumour edge for panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs and [<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Radiation nanomedicines incorporating the AE-emitter, <jats:sup>197<\/jats:sup>Hg administered by CED are a promising approach to treatment of GBM. Panitumumab-[<jats:sup>197<\/jats:sup>Hg]Hg-AuNPs are particularly attractive due to their EGFR-mediated binding, internalization and nuclear importation in GBM cells, which amplifies their in vitro cytotoxicity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s41181-025-00367-2","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T19:49:11Z","timestamp":1752781751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Auger electron-emitting EGFR-targeted and non-targeted [197Hg]Hg-gold nanoparticles for treatment of glioblastoma multiforme (GBM)"],"prefix":"10.1186","volume":"10","author":[{"given":"Madeline K.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongli","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine J.","family":"Georgiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeela","family":"Ganga-Sah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Radchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Rutka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-7993","authenticated-orcid":false,"given":"Raymond M.","family":"Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"issue":"15","key":"367_CR1","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1021\/acs.molpharmaceut.7b01000","volume":"2018","author":"S Aghevlian","year":"2018","unstructured":"Aghevlian S, Lu Y, Winnik MA, Hedley DW, Reilly RM. 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