{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:04:04Z","timestamp":1789671844568,"version":"4.0.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["12567"],"award-info":[{"award-number":["12567"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["09150172010054"],"award-info":[{"award-number":["09150172010054"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Imaging Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Tumor hypoxia correlates with a poor prognosis in many solid tumors, including head and neck squamous cell carcinoma (HNSCC). Carbonic anhydrase IX (CAIX) is an endogenous hypoxia-related marker and can be targeted using the humanized monoclonal antibody girentuximab (hG250). A potential new therapy to treat hypoxic tumors is CAIX-targeted \u03b1 therapy (CAIX-TAT) as \u03b1-particles cause complex DNA damage independent of oxygen levels. Here, we investigate the targeting potential of CAIX-TAT in patient-derived HNSCC SCCNij153 xenografts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      DOTA-hG250 was labeled with indium-111 (\n                      <jats:sup>111<\/jats:sup>\n                      In) or actinium-225 (\n                      <jats:sup>225<\/jats:sup>\n                      Ac), and\n                      <jats:italic>in vivo<\/jats:italic>\n                      biodistribution was assessed in SCCNij153 tumor-bearing mice. The spatial distribution of radiolabeled hG250 was correlated to CAIX expression using autoradiography and immunofluorescence. Absorbed doses of [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-DOTA-hG250 in healthy tissue and CAIX-positive (CAIX+) tumor regions were calculated from\n                      <jats:italic>ex vivo<\/jats:italic>\n                      biodistribution data and quantitative longitudinal SPECT imaging. Finally, SCCNij153 tumor sections from mice injected with [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-DOTA-hG250 were stained for the DNA damage marker \u03b3H2AX.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-DOTA-hG250 accumulates in SCCNij153 tumors 3\u00a0days after injection (25.4\u2009\u00b1\u20095.0\u00a0%IA\/g). Autoradiography and CAIX immunofluorescence of\n                      <jats:italic>ex vivo<\/jats:italic>\n                      tumor tissue shows that this uptake is predominantly present in the CAIX+\u2009tumor areas. Dosimetry calculations indicated that treatment with 15\u00a0kBq [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-DOTA-hG250 would result in an absorbed dose of 92.5\u2009\u00b1\u200935.4\u00a0Gy for CAIX+\u2009tumor areas. Tumor sections obtained 7\u00a0days after [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-DOTA-hG250 showed that\n                      <jats:sup>225<\/jats:sup>\n                      Ac colocalized with CAIX expression and a trend was observed towards more \u03b3H2AX foci compared with DOTA-hG250 injected mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Radiolabeled hG250 binds to CAIX+\u2009tumor regions in SCCNij153 tumor-bearing mice. Additional studies are required to assess the therapeutic potential and underlying mechanism-of-action of CAIX-TAT for hypoxic tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11307-026-02142-4","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:20:47Z","timestamp":1789669247000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proof-of-Concept of CAIX-Targeted \u03b1-Particle Delivery in a Patient-Derived Hypoxic Head and Neck Squamous Cell Carcinoma Model"],"prefix":"10.1007","author":[{"given":"Sylvia T. M.","family":"Wenker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben M.","family":"Franssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke D. 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Sandra Heskamp is an inventor on the patent \u2018PSMA-targeting ligands for multimodal applications\u2019 and on a patent involving the combination of [\n                      177\n                      Lu]Lu-DOTA-hG250 with immune checkpoint inhibitor therapy. The other authors declare that they have no competing interests.","order":1,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}