{"entity": "publication", "iuid": "9d46df5f4d594f878c5147de82013fc3", "timestamp": "2026-08-22T08:30:43.535Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9d46df5f4d594f878c5147de82013fc3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9d46df5f4d594f878c5147de82013fc3"}}, "title": "Molecular Design of HER3-Targeting Affibody Molecules: Influence of Chelator and Presence of HEHEHE-Tag on Biodistribution of 68Ga-Labeled Tracers.", "authors": [{"family": "Dahlsson Leitao", "given": "Charles", "initials": "C"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Andersson", "given": "Ken G", "initials": "KG"}, {"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": "2019-03-02", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "20", "issue": "5", "issn-l": null}, "abstract": "Affibody-based imaging of HER3 is a promising approach for patient stratification. We investigated the influence of a hydrophilic HEHEHE-tag ((HE)\u2083-tag) and two different gallium-68/chelator-complexes on the biodistribution of Z08698 with the aim to improve the tracer for PET imaging. Affibody molecules (HE)\u2083-Z08698-X and Z08698-X (X = NOTA, NODAGA) were produced and labeled with gallium-68. Binding specificity and cellular processing were studied in HER3-expressing human cancer cell lines BxPC-3 and DU145. Biodistribution was studied 3 h p.i. in Balb/c nu/nu mice bearing BxPC-3 xenografts. Mice were imaged 3 h p.i. using microPET/CT. Conjugates were stably labeled with gallium-68 and bound specifically to HER3 in vitro and in vivo. Association to cells was rapid but internalization was slow. Uptake in tissues, including tumors, was lower for (HE)\u2083-Z08698-X than for non-tagged variants. The neutral [68Ga]Ga-NODAGA complex reduced the hepatic uptake of Z08698 compared to positively charged [68Ga]Ga-NOTA-conjugated variants. The influence of the chelator was more pronounced in variants without (HE)3-tag. In conclusion, hydrophilic (HE)\u2083-tag and neutral charge of the [68Ga]Ga-NODAGA complex promoted blood clearance and lowered hepatic uptake of Z08698. [68Ga]Ga-(HE)\u2083-Z08698-NODAGA was considered most promising, providing the lowest blood and hepatic uptake and the best imaging contrast among the tested variants.", "doi": "10.3390/ijms20051080", "pmid": "30832342", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6429182"}, {"db": "pii", "key": "ijms20051080"}], "notes": [], "created": "2026-08-21T13:02:57.420Z", "modified": "2026-08-21T13:02:57.495Z"}