{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:38:36Z","timestamp":1791308316526,"version":"4.3.1"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["23 2645 PjF 01H"],"award-info":[{"award-number":["23 2645 PjF 01H"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["CAN 21 1485"],"award-info":[{"award-number":["CAN 21 1485"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["243657 Pj"],"award-info":[{"award-number":["243657 Pj"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2022-00556"],"award-info":[{"award-number":["2022-00556"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2023-02158"],"award-info":[{"award-number":["2023-02158"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003748","name":"Svenska S\u00e4llskapet f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","award":["PG-22-0350-H-01"],"award-info":[{"award-number":["PG-22-0350-H-01"]}],"id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>B7-H3 (CD276), an immune checkpoint protein, is overexpressed in malignant tumors, while its expression in normal tissues is low, and several B7-H3-targeting therapies are under clinical evaluation. Radionuclide molecular imaging offers a non-invasive method for determining B7-H3 expression levels and may aid in improved patient selection. The feasibility of the use of Affibody molecules for the visualization of B7-H3 was demonstrated earlier. The selection of an approach for routine labeling providing high radiochemical yields and reproducibility is, however, critical for successful clinical translation. The optimal combination of a targeting protein, chelator\/linker, and radionuclide should provide high-contrast visualization. In this study, we evaluated an acyclic chelator, tris(3,4-hydroxypyridinone) (THP), for labeling of the Affibody molecule ZB7-H3_2 with 68Ga and compared its impact on radiolabeling efficiency and targeting properties with the impact of the cyclic chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Maleimide derivatives of THP and NOTA were site-specifically coupled to the C-terminal cysteine of ZB7-H3_2. THP-ZB7-H3_2 was successfully labeled with 68Ga within 5 min of incubation at room temperature, achieving a 100% radiochemical yield. NOTA-ZB7-H3 required heating at 60 \u00b0C for 10 min, and the radiochemical yield was lower. Both radioconjugates exhibited specific binding to B7-H3-expressing cells with similar binding strength, and both tracers demonstrated similar tumor uptake (p &gt; 0.05) in a murine model. The biodistribution was similar, although [68Ga]Ga-NOTA-ZB7-H3_2 provided slightly but significantly higher tumor-to-liver and tumor-to-spleen ratios. Nonetheless, the advantages of THP include rapid and mild radiolabeling with high efficiency, eliminating the need for heating and a post-purification step, which suggests a potential for streamlined clinical translation of ZB7-H3_2.<\/jats:p>","DOI":"10.3390\/ijms27041713","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:16:08Z","timestamp":1770801368000},"page":"1713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficient 68Ga Labeling of a B7-H3-Targeting Affibody Molecule via Acyclic Tris(hydroxypyridinone) Chelator: Effects on Biodistribution in a Preclinical Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6122-1734","authenticated-orcid":false,"given":"Vladimir","family":"Tolmachev","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelinda Janice","family":"Herlina","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5340-8618","authenticated-orcid":false,"given":"Eleftherios","family":"Papalanis","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7699-5719","authenticated-orcid":false,"given":"Ekaterina","family":"A. Bezverkhniaia","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Uppsala University, 751 83 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Ryer","sequence":"additional","affiliation":[{"name":"Affibody AB, 171 65 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-2683","authenticated-orcid":false,"given":"Anna","family":"Orlova","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Uppsala University, 751 83 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Y. Frejd","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden"},{"name":"Affibody AB, 171 65 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2660-9837","authenticated-orcid":false,"given":"Maryam","family":"Oroujeni","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1158\/1078-0432.CCR-20-2584","article-title":"B7-H3: An Attractive Target for Antibody-based Immunotherapy","volume":"27","author":"Kontos","year":"2021","journal-title":"Clin. 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