{"entity": "researcher", "timestamp": "2026-08-22T07:49:12.120Z", "family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "affiliations": ["Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb"}}, "publications": [{"entity": "publication", "iuid": "5f65ced79c3b40ea96ee5e9e78ca4d73", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5f65ced79c3b40ea96ee5e9e78ca4d73.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5f65ced79c3b40ea96ee5e9e78ca4d73"}}, "title": "Targeting Tumor Cells Overexpressing the Human Epidermal Growth Factor Receptor 3 with Potent Drug Conjugates Based on Affibody Molecules.", "authors": [{"family": "Rinne", "given": "Sara S", "initials": "SS", "orcid": "0000-0003-2141-3982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3aea3edd98b441c98bb527b1e0c911f5.json"}}, {"family": "Yin", "given": "Wen", "initials": "W"}, {"family": "Borras", "given": "Anna Mestre", "initials": "AM"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb.json"}}, {"family": "St\u00e5hl", "given": "Stefan", "initials": "S"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.json"}}], "type": "journal article", "published": "2022-05-31", "journal": {"title": "Biomedicines", "issn": "2227-9059", "volume": "10", "issue": "6", "issn-l": null}, "abstract": "Increasing evidence suggests that therapy targeting the human epidermal growth factor receptor 3 (HER3) could be a viable route for targeted cancer therapy. Here, we studied a novel drug conjugate, ZHER3-ABD-mcDM1, consisting of a HER3-targeting affibody molecule, coupled to the cytotoxic tubulin polymerization inhibitor DM1, and an albumin-binding domain for in vivo half-life extension. ZHER3-ABD-mcDM1 showed a strong affinity to the extracellular domain of HER3 (KD 6 nM), and an even stronger affinity (KD 0.2 nM) to the HER3-overexpressing pancreatic carcinoma cell line, BxPC-3. The drug conjugate showed a potent cytotoxic effect on BxPC-3 cells with an IC50 value of 7 nM. Evaluation of a radiolabeled version, [99mTc]Tc-ZHER3-ABD-mcDM1, showed a relatively high rate of internalization, with a 27% internalized fraction after 8 h. Further in vivo evaluation showed that it could target BxPC-3 (pancreatic carcinoma) and DU145 (prostate carcinoma) xenografts in mice, with an uptake peaking at 6.3 \u00b1 0.4% IA/g at 6 h post-injection for the BxPC-3 xenografts. The general biodistribution showed uptake in the liver, lung, salivary gland, stomach, and small intestine, organs known to express murine ErbB3 naturally. The results from the study show that ZHER3-ABD-mcDM1 is a highly potent and selective drug conjugate with the ability to specifically target HER3 overexpressing cells. Further pre-clinical and clinical development is discussed.", "doi": "10.3390/biomedicines10061293", "pmid": "35740315", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9219639"}, {"db": "pii", "key": "biomedicines10061293"}], "notes": [], "created": "2026-08-21T13:01:13.994Z", "modified": "2026-08-21T13:01:14.186Z"}, {"entity": "publication", "iuid": "c79424bdacc14f898c66b0a94fcae8c8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c79424bdacc14f898c66b0a94fcae8c8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c79424bdacc14f898c66b0a94fcae8c8"}}, "title": "HER3 PET Imaging: 68Ga-Labeled Affibody Molecules Provide Superior HER3 Contrast to 89Zr-Labeled Antibody and Antibody-Fragment-Based Tracers.", "authors": [{"family": "Rinne", "given": "Sara S", "initials": "SS", "orcid": "0000-0003-2141-3982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3aea3edd98b441c98bb527b1e0c911f5.json"}}, {"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"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": "2021-09-24", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "19", "issn-l": "2072-6694"}, "abstract": "HER3 (human epidermal growth factor receptor type 3) is a challenging target for diagnostic radionuclide molecular imaging due to the relatively modest overexpression in tumors and substantial expression in healthy organs. In this study, we compared four HER3-targeting PET tracers based on different types of targeting molecules in a preclinical model: the 89Zr-labeled therapeutic antibody seribantumab, a seribantumab-derived F(ab)2-fragment labeled with 89Zr and 68Ga, and the 68Ga-labeled affibody molecule [68Ga]Ga-ZHER3. The novel conjugates were radiolabeled and characterized in vitro using HER3-expressing BxPC-3 and DU145 human cancer cells. Biodistribution was studied using Balb/c nu/nu mice bearing BxPC-3 xenografts. HER3-negative RAMOS xenografts were used to demonstrate binding specificity in vivo. Autoradiography was conducted on the excised tumors. nanoPET/CT imaging was performed. New conjugates specifically bound to HER3 in vitro and in vivo. [68Ga]Ga-DFO-seribantumab-F(ab')2 was considered unsuitable for imaging due to the low stability and high uptake in normal organs. The highest tumor-to-non-tumor contrast with [89Zr]Zr-DFO-seribantumab and [89Zr]Zr-DFO-seribantumab-F(ab')2 was achieved at 96 h and 48 h pi, respectively. Despite lower tumor uptake, [68Ga]Ga-ZHER3 provided the best imaging contrast due to the fastest clearance from blood and normal organs. The results of our study suggest that affibody-based tracers are more suitable for PET imaging of HER3 expression than antibody- and antibody-fragment-based tracers.", "doi": "10.3390/cancers13194791", "pmid": "34638277", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8508546"}, {"db": "pii", "key": "cancers13194791"}], "notes": [], "created": "2026-08-21T13:01:47.341Z", "modified": "2026-08-21T13:01:47.376Z"}, {"entity": "publication", "iuid": "70d8595b7f524892aced629b61e2eba4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/70d8595b7f524892aced629b61e2eba4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/70d8595b7f524892aced629b61e2eba4"}}, "title": "Evaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model.", "authors": [{"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Vorontsova", "given": "Olga", "initials": "O"}, {"family": "Dun\u00e5s", "given": "Finn", "initials": "F"}, {"family": "Jonasson", "given": "Per", "initials": "P"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb.json"}}, {"family": "St\u00e5hl", "given": "Stefan", "initials": "S"}, {"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": "2020-06-13", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "12", "issue": "6", "issn-l": null}, "abstract": "Human epidermal growth factor receptor 3 (HER3) has been increasingly scrutinized as a potential drug target since the elucidation of its role in mediating tumor growth and acquired therapy resistance. Affibody molecules are so-called scaffold proteins with favorable biophysical properties, such as a small size for improved tissue penetration and extravasation, thermal and chemical stability, and a high tolerance to modifications. Additionally, affibody molecules are efficiently produced in prokaryotic hosts or by chemical peptide synthesis. We have previously evaluated the biodistribution profiles of five mono- and bivalent anti-HER3 affibody molecules (designated as 3) fused to an albumin-binding domain (designated as A), 3A, 33A, 3A3, A33, and A3, that inhibit ligand-dependent phosphorylation. In the present study, we examined the therapeutic efficacy of the three most promising variants, 3A, 33A, and 3A3, in a direct comparison with the HER3-targeting monoclonal antibody seribantumab (MM-121) in a preclinical BxPC-3 pancreatic cancer model. Xenografted mice were treated with either an affibody construct or MM-121 and the tumor growth was compared to a vehicle group. Receptor occupancy was estimated by positron emission tomography/computed tomography (PET/CT) imaging using a HER3-targeting affibody imaging agent [68Ga]Ga-(HE)3-Z08698-NODAGA. The affibody molecules could inhibit ligand-dependent phosphorylation and cell proliferation in vitro and demonstrated tumor growth inhibition in vivo comparable to that of MM-121. PET/CT imaging showed full receptor occupancy for all tested drug candidates. Treatment with 3A and 3A3 affibody constructs was more efficient than with 33A and similar to the anti-HER3 antibody seribantumab, showing that the molecular design of affibody-based therapeutics targeting HER3 in terms of the relative position of functional domains and valency has an impact on therapeutic effect.", "doi": "10.3390/pharmaceutics12060551", "pmid": "32545760", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7356278"}, {"db": "pii", "key": "pharmaceutics12060551"}], "notes": [], "created": "2026-08-21T13:04:42.755Z", "modified": "2026-08-21T13:04:42.820Z"}, {"entity": "publication", "iuid": "9b21fb72055b446c864df7a2b2775413", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9b21fb72055b446c864df7a2b2775413.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9b21fb72055b446c864df7a2b2775413"}}, "title": "Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules.", "authors": [{"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Dahlsson Leitao", "given": "Charles", "initials": "C"}, {"family": "Saleh-Nihad", "given": "Zahra", "initials": "Z"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"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": "2020-03-13", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "21", "issue": "6", "issn-l": null}, "abstract": "HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt-chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)3-ZHER3 and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)3-ZHER3-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [57Co]Co (surrogate for 55Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [57Co]Co-(HE)3-ZHER3-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA 3 h pi, [57Co]Co-(HE)3-ZHER3-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [57Co]Co-chelator complex influenced the uptake in tumors and normal tissue. [57Co]Co-(HE)3-ZHER3-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [57Co]Co-(HE)3-ZHER3-DOTA improved imaging contrast compared to early-time-point imaging with [68Ga]Ga-(HE)3-ZHER3-NODAGA.", "doi": "10.3390/ijms21061972", "pmid": "32183096", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7139902"}, {"db": "pii", "key": "ijms21061972"}], "notes": [], "created": "2026-08-21T13:03:08.958Z", "modified": "2026-08-21T13:03:08.988Z"}, {"entity": "publication", "iuid": "8d1411b7582d4c8c859ddfae66998a24", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8d1411b7582d4c8c859ddfae66998a24.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8d1411b7582d4c8c859ddfae66998a24"}}, "title": "Influence of Residualizing Properties of the Radiolabel on Radionuclide Molecular Imaging of HER3 Using Affibody Molecules.", "authors": [{"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Xu", "given": "Tianqi", "initials": "T"}, {"family": "Dahlsson Leitao", "given": "Charles", "initials": "C"}, {"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"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}], "type": "journal article", "published": "2020-02-15", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "21", "issue": "4", "issn-l": null}, "abstract": "Human epidermal growth factor receptor type 3 (HER3) is an emerging therapeutic target in several malignancies. To select potential responders to HER3-targeted therapy, radionuclide molecular imaging of HER3 expression using affibody molecules could be performed. Due to physiological expression of HER3 in normal organs, high imaging contrast remains challenging. Due to slow internalization of affibody molecules by cancer cells, we hypothesized that labeling (HE)3-ZHER3:08698-DOTAGA affibody molecule with non-residualizing [125I]-N-succinimidyl-4-iodobenzoate (PIB) label would improve the tumor-to-normal organs ratios compared to previously reported residualizing radiometal labels. The [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA was compared side-by-side with [111In]In-(HE)3-ZHER3:08698-DOTAGA. Both conjugates demonstrated specific high-affinity binding to HER3-expressing BxPC-3 and DU145 cancer cells. Biodistribution in mice bearing BxPC-3 xenografts at 4 and 24 h pi showed faster clearance of the [125I]I-PIB label compared to the indium-111 label from most tissues, except blood. This resulted in higher tumor-to-organ ratios in HER3-expressing organs for [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA at 4 h, providing the tumor-to-liver ratio of 2.4 \u00b1 0.3. The tumor uptake of both conjugates was specific, however, it was lower for the [125I]I-PIB label. In conclusion, the use of non-residualizing [125I]I-PIB label for HER3-targeting affibody molecule provided higher tumor-to-liver ratio than the indium-111 label, however, further improvement in tumor uptake and retention is needed.", "doi": "10.3390/ijms21041312", "pmid": "32075258", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7072899"}, {"db": "pii", "key": "ijms21041312"}], "notes": [], "created": "2026-08-21T13:03:04.464Z", "modified": "2026-08-21T13:03:04.541Z"}, {"entity": "publication", "iuid": "b3bf3e73d7104ff191f2c382148b55d6", "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"}, {"entity": "publication", "iuid": "e4e9d94ba60d4c2399b5b7e2d7d151e3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e4e9d94ba60d4c2399b5b7e2d7d151e3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e4e9d94ba60d4c2399b5b7e2d7d151e3"}}, "title": "Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3.", "authors": [{"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Schulga", "given": "Alexey", "initials": "A"}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "G\u00fcler", "given": "Rezan", "initials": "R"}, {"family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb.json"}}, {"family": "Sandstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Garousi", "given": "Javad", "initials": "J"}, {"family": "Chernov", "given": "Vladimir", "initials": "V"}, {"family": "Bragina", "given": "Olga", "initials": "O"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Deyev", "given": "Sergey M", "initials": "SM"}], "type": "journal article", "published": "2019-06-28", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "9", "issue": "1", "pages": "9405", "issn-l": "2045-2322"}, "abstract": "Radionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARPin G3, a small (14 kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE)3) of histidine-containing tags would influence the biodistribution of [99mTc]Tc(CO)3-labeled DARPin G3. To test the hypothesis, G3 variants containing tags at N-terminus (H6-G3 and (HE)3-G3) or at C-terminus (G3-H6 and G3-(HE)3) were labeled with [99mTc]Tc(CO)3. Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [99mTc]Tc(CO)3-labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [99mTc]Tc(CO)3-(HE)3-G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [99mTc]Tc(CO)3-(HE)3-G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites.", "doi": "10.1038/s41598-019-45795-8", "pmid": "31253840", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6599047"}, {"db": "pii", "key": "10.1038/s41598-019-45795-8"}], "notes": [], "created": "2026-08-21T11:52:49.253Z", "modified": "2026-08-21T11:52:49.317Z"}, {"entity": "publication", "iuid": "cd8e33b5ca8646c89517bcb93a190f79", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cd8e33b5ca8646c89517bcb93a190f79.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cd8e33b5ca8646c89517bcb93a190f79"}}, "title": "Improved contrast of affibody-mediated imaging of HER3 expression in mouse xenograft model through co-injection of a trivalent affibody for in vivo blocking of hepatic uptake.", "authors": [{"family": "Rosestedt", "given": "Maria", "initials": "M"}, {"family": "Andersson", "given": "Ken G", "initials": "KG"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"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": "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": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.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": "2019-05-01", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "9", "issue": "1", "pages": "6779", "issn-l": "2045-2322"}, "abstract": "Human epidermal growth factor receptor type 3 (HER3) plays a crucial role in the progression of many cancer types. In vivo radionuclide imaging could be a reliable method for repetitive detection of HER3-expression in tumors. The main challenge of HER3-imaging is the low expression in tumors together with endogenous receptor expression in normal tissues, particularly the liver. A HER3-targeting affibody molecule labeled with radiocobalt via a NOTA chelator [57Co]Co-NOTA-Z08699 has demonstrated the most favorable biodistribution profile with the lowest unspecific hepatic uptake and high activity uptake in tumors. We hypothesized that specific uptake of labeled affibody monomer might be selectively blocked in the liver but not in tumors by a co-injection of non-labeled corresponding trivalent affibody (Z08699)3. Biodistribution of [57Co]Co-NOTA-Z08699 and [111In]In-DOTA-(Z08699)3 was studied in BxPC-3 xenografted mice. [57Co]Co-NOTA-Z08699 was co-injected with unlabeled trivalent affibody DOTA-(Z08699)3 at different monomer:trimer molar ratios. HER3-expression in xenografts was imaged using [57Co]Co-NOTA-Z08699 and [57Co]Co-NOTA-Z08699: DOTA-(Z08699)3. Hepatic activity uptake of [57Co]Co-NOTA-Z08699: DOTA-(Z08699)3 decreased with increasing monomer:trimer molar ratio. The tumor activity uptake and tumor-to-liver ratios were the highest for the 1:3 ratio. SPECT/CT images confirmed the biodistribution data. Imaging of HER3 expression can be improved by co-injection of a radiolabeled monomeric affibody-based imaging probe together with a trivalent affibody.", "doi": "10.1038/s41598-019-43145-2", "pmid": "31043683", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6494909"}, {"db": "pii", "key": "10.1038/s41598-019-43145-2"}], "notes": [], "created": "2026-08-21T11:52:46.575Z", "modified": "2026-08-21T11:52:46.671Z"}, {"entity": "publication", "iuid": "9d46df5f4d594f878c5147de82013fc3", "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"}, {"entity": "publication", "iuid": "e9ba7b5d6e1240168e0321a0362b6fd3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e9ba7b5d6e1240168e0321a0362b6fd3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e9ba7b5d6e1240168e0321a0362b6fd3"}}, "title": "Optimization of HER3 expression imaging using affibody molecules: Influence of chelator for labeling with indium-111.", "authors": [{"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Bass", "given": "Tarek Z", "initials": "TZ", "orcid": "0000-0003-1598-8894", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0291a38a362242828bd1ca877a9c8372.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": "2019-01-24", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "9", "issue": "1", "pages": "655", "issn-l": "2045-2322"}, "abstract": "Radionuclide molecular imaging of human epidermal growth factor receptor 3 (HER3) expression using affibody molecules could be used for patient stratification for HER3-targeted cancer therapeutics. We hypothesized that the properties of HER3-targeting affibody molecules might be improved through modification of the radiometal-chelator complex. Macrocyclic chelators NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid), NODAGA (1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), and DOTAGA (1,4,7,10-tetraazacyclododececane,1-(glutaric acid)-4,7,10-triacetic acid) were conjugated to the C-terminus of anti-HER3 affibody molecule Z08698 and conjugates were labeled with indium-111. All conjugates bound specifically and with picomolar affinity to HER3 in vitro. In mice bearing HER3-expressing xenografts, no significant difference in tumor uptake between the conjugates was observed. Presence of the negatively charged 111In-DOTAGA-complex resulted in the lowest hepatic uptake and the highest tumor-to-liver ratio. In conclusion, the choice of chelator influences the biodistribution of indium-111 labeled anti-HER3 affibody molecules. Hepatic uptake of anti-HER3 affibody molecules could be reduced by the increase of negative charge of the radiometal-chelator complex on the C-terminus without significantly influencing the tumor uptake.", "doi": "10.1038/s41598-018-36827-w", "pmid": "30679757", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6345776"}, {"db": "pii", "key": "10.1038/s41598-018-36827-w"}], "notes": [], "created": "2026-08-21T11:52:40.052Z", "modified": "2026-08-21T11:52:40.223Z"}, {"entity": "publication", "iuid": "35f3af168750431dadf2fe12e5279a36", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/35f3af168750431dadf2fe12e5279a36.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/35f3af168750431dadf2fe12e5279a36"}}, "title": "Influence of Molecular Design on the Targeting Properties of ABD-Fused Mono- and Bi-Valent Anti-HER3 Affibody Therapeutic Constructs.", "authors": [{"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Atterby", "given": "Christina", "initials": "C"}, {"family": "St\u00e5hl", "given": "Stefan", "initials": "S"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"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": "2018-10-11", "journal": {"title": "Cells", "issn": "2073-4409", "volume": "7", "issue": "10", "issn-l": "2073-4409"}, "abstract": "Overexpression of human epidermal growth factor receptor type 3 (HER3) is associated with tumour cell resistance to HER-targeted therapies. Monoclonal antibodies (mAbs) targeting HER3 are currently being investigated for treatment of various types of cancers. Cumulative evidence suggests that affibody molecules may be appropriate alternatives to mAbs. We previously reported a fusion construct (3A3) containing two HER3-targeting affibody molecules flanking an engineered albumin-binding domain (ABD035) included for the extension of half-life in circulation. The 3A3 fusion protein (19.7 kDa) was shown to delay tumour growth in mice bearing HER3-expressing xenografts and was equipotent to the mAb seribantumab. Here, we have designed and explored a series of novel formats of anti-HER3 affibody molecules fused to the ABD in different orientations. All constructs inhibited heregulin-induced phosphorylation in HER3-expressing BxPC-3 and DU-145 cell lines. Biodistribution studies demonstrated extended the half-life of all ABD-fused constructs, although at different levels. The capacity of our ABD-fused proteins to accumulate in HER3-expressing tumours was demonstrated in nude mice bearing BxPC-3 xenografts. Formats where the ABD was located on the C-terminus of affibody binding domains (3A, 33A, and 3A3) provided the best tumour targeting properties in vivo. Further development of these promising candidates for treatment of HER3-overexpressing tumours is therefore justified.", "doi": "10.3390/cells7100164", "pmid": "30314301", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6210767"}, {"db": "pii", "key": "cells7100164"}], "notes": [], "created": "2026-08-21T13:02:23.005Z", "modified": "2026-08-21T13:02:23.074Z"}]}