{"entity": "publication", "iuid": "b3bf3e73d7104ff191f2c382148b55d6", "timestamp": "2026-08-22T08:30:49.222Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b3bf3e73d7104ff191f2c382148b55d6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b3bf3e73d7104ff191f2c382148b55d6"}}, "title": "Increase in negative charge of 68Ga/chelator complex reduces unspecific hepatic uptake but does not improve imaging properties of HER3-targeting affibody molecules.", "authors": [{"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Dahlsson Leitao", "given": "Charles", "initials": "C"}, {"family": "Gentry", "given": "Joshua", "initials": "J"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "St\u00e5hl", "given": "Stefan", "initials": "S"}, {"family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb.json"}}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2019-11-27", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "9", "issue": "1", "pages": "17710", "issn-l": "2045-2322"}, "abstract": "Upregulation of the human epidermal growth factor receptor type 3 (HER3) is a common mechanism to bypass HER-targeted cancer therapy. Affibody-based molecular imaging has the potential for detecting and monitoring HER3 expression during treatment. In this study, we compared the imaging properties of newly generated 68Ga-labeled anti-HER3 affibody molecules (HE)3-ZHER3-DOTA and (HE)3-ZHER3-DOTAGA with previously reported [68Ga]Ga-(HE)3-ZHER3-NODAGA. We hypothesized that increasing the negative charge of the gallium-68/chelator complex would reduce hepatic uptake, which could lead to improved contrast of anti-HER3 affibody-based PET-imaging of HER3 expression. (HE)3-ZHER3-X (X = DOTA, DOTAGA) were produced and labeled with gallium-68. Binding of the new conjugates was specific in HER3 expressing BxPC-3 and DU145 human cancer cells. Biodistribution and in vivo specificity was studied in BxPC-3 xenograft bearing Balb/c nu/nu mice 3 h pi. DOTA- and DOTAGA-containing conjugates had significantly higher concentration in blood than [68Ga]Ga-(HE)3-ZHER3-NODAGA. Presence of the negatively charged 68Ga-DOTAGA complex reduced the unspecific hepatic uptake, but did not improve overall biodistribution of the conjugate. [68Ga]Ga-(HE)3-ZHER3-DOTAGA and [68Ga]Ga-(HE)3-ZHER3-NODAGA had similar tumor-to-liver ratios, but [68Ga]Ga-(HE)3-ZHER3-NODAGA had the highest tumor uptake and tumor-to-blood ratio among the tested conjugates. In conclusion, [68Ga]Ga-(HE)3-ZHER3-NODAGA remains the favorable variant for PET imaging of HER3 expression.", "doi": "10.1038/s41598-019-54149-3", "pmid": "31776413", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6881397"}, {"db": "pii", "key": "10.1038/s41598-019-54149-3"}], "notes": [], "created": "2026-08-21T11:52:55.742Z", "modified": "2026-08-21T11:52:55.818Z"}