{"entity": "researcher", "timestamp": "2026-08-22T07:47:59.521Z", "family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "affiliations": ["Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134"}}, "publications": [{"entity": "publication", "iuid": "8dd62b52564244adb5b31b41d3dad8c8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8dd62b52564244adb5b31b41d3dad8c8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8dd62b52564244adb5b31b41d3dad8c8"}}, "title": "Preclinical Evaluation of a Novel High-Affinity Radioligand [99mTc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA).", "authors": [{"family": "Bezverkhniaia", "given": "Ekaterina", "initials": "E", "orcid": "0000-0001-7699-5719", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/211d24252bc84d43aed1d7ed4c3d3238.json"}}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Larkina", "given": "Mariia", "initials": "M", "orcid": "0000-0003-1176-2441", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/557c8a9c8b2142a7a88d6211335d24e4.json"}}, {"family": "Oroujeni", "given": "Maryam", "initials": "M", "orcid": "0000-0003-2660-9837", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bdd7a76401c42b4bbe8b11cfdb83212.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec6820fcb786475d85969630b0b3860b.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": "2023-12-12", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "24", "issue": "24", "issn-l": null}, "abstract": "Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl-triglutamate chelator for labeling with Tc-99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [99mTc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [99mTc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [99mTc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 \u00b1 15 pM. In tumor-bearing mice, the tumor uptake of [99mTc]Tc-BQ0413 (38 \u00b1 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 \u00b1 2 %IA/g and 0.9 \u00b1 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [99mTc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [99mTc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT).", "doi": "10.3390/ijms242417391", "pmid": "38139219", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10743726"}, {"db": "pii", "key": "ijms242417391"}], "notes": [], "created": "2026-08-21T13:03:48.635Z", "modified": "2026-08-21T13:03:48.835Z"}, {"entity": "publication", "iuid": "4141afd0a66b44d183c7467bdf4893e1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4141afd0a66b44d183c7467bdf4893e1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4141afd0a66b44d183c7467bdf4893e1"}}, "title": "Feasibility of Co-Targeting HER3 and EpCAM Using Seribantumab and DARPin-Toxin Fusion in a Pancreatic Cancer Xenograft Model.", "authors": [{"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"family": "Schulga", "given": "Alexey", "initials": "A", "orcid": "0000-0003-3425-0828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45b1c8e5447c41bbb93e61706377a0c7.json"}}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Rinne", "given": "Sara S", "initials": "SS", "orcid": "0000-0003-2141-3982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3aea3edd98b441c98bb527b1e0c911f5.json"}}, {"family": "Zhang", "given": "Hongchao", "initials": "H"}, {"family": "Vorontsova", "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": "Deyev", "given": "Sergey M", "initials": "SM", "orcid": "0000-0002-3952-0631", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb88df2aaa8a46a5957370b9258e2834.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": "2023-02-02", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "24", "issue": "3", "issn-l": null}, "abstract": "Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1-LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled 99mTc(CO)3-Ec1-LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1-LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1-LoPE and MM-121 in vitro. An experimental therapy study using Ec1-LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified.", "doi": "10.3390/ijms24032838", "pmid": "36769161", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9917732"}, {"db": "pii", "key": "ijms24032838"}], "notes": [], "created": "2026-08-21T13:03:41.482Z", "modified": "2026-08-21T13:03:41.558Z"}, {"entity": "publication", "iuid": "4b3601a31bff41d098969d0865e1fca6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4b3601a31bff41d098969d0865e1fca6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4b3601a31bff41d098969d0865e1fca6"}}, "title": "Biologic Evaluation of a Heterodimeric HER2-Albumin Targeted Affibody Molecule Produced by Chemo-Enzymatic Peptide Synthesis.", "authors": [{"family": "Liu", "given": "Yongsheng", "initials": "Y", "orcid": "0000-0001-5871-5779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a53363bbcb5b414681ee46ac22b65230.json"}}, {"family": "G\u00fcler", "given": "Rezan", "initials": "R"}, {"family": "Liao", "given": "Yunqi", "initials": "Y", "orcid": "0000-0001-6038-8295", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/64779a498ff845a1830ff4b7940e3a3b.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Widmark", "given": "Olof", "initials": "O"}, {"family": "Meuleman", "given": "Theodorus J", "initials": "TJ"}, {"family": "Koijen", "given": "Anna", "initials": "A", "orcid": "0000-0003-2375-334X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/66e585ae6a98407197c25037d047c6c6.json"}}, {"family": "van den Bos", "given": "Leendert J", "initials": "LJ", "orcid": "0000-0003-2410-5838", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac800f8ae2a44b1981e811efc53614e1.json"}}, {"family": "Naasz", "given": "Robert", "initials": "R"}, {"family": "Bodenko", "given": "Vitalina", "initials": "V"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Ekblad", "given": "Caroline", "initials": "C"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Frejd", "given": "Fredrik Y", "initials": "FY", "orcid": "0000-0002-6421-4142", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0bf87385618f44ddae90e48177849e4e.json"}}], "type": "journal article", "published": "2022-11-19", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "14", "issue": "11", "issn-l": null}, "abstract": "Targeted molecular radiation therapy is a promising emerging treatment modality in oncology, and peptide synthesis may shorten the time to reach the clinical stage. In this study, we have explored Chemo-Enzymatic Peptide Synthesis, or CEPS, as a new means of producing a therapeutic HER2 targeted Affibody\u00ae molecule, comprising a C-terminal albumin binding domain (ABD) for half-life extension and a total length of 108 amino acids. In addition, a DOTA moiety could be incorporated at N-terminus directly during the synthesis step and subsequently utilized for site-specific radiolabeling with the therapeutic radionuclide 177Lu. Retained thermodynamic stability as well as retained binding to both HER2 and albumin was verified. Furthermore, HER2 binding specificity of the radiolabeled Affibody molecule was confirmed by an in vitro saturation assay showing a significantly higher cell-bound activity of SKOV-3 (high HER2 expression) compared with BxPC3 (low HER2 expression), both in the presence and absence of HSA. In vivo evaluation in mice bearing HER2 expressing xenografts also showed specific tumor targeting as well as extended time in circulation and reduced kidney uptake compared with a HER2 targeted Affibody molecule without the ABD moiety. To conclude, we have demonstrated that CEPS can be used for production of Affibody-fusion molecules with retained in vitro and in vivo functionality.", "doi": "10.3390/pharmaceutics14112519", "pmid": "36432709", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9698269"}, {"db": "pii", "key": "pharmaceutics14112519"}], "notes": [], "created": "2026-08-21T13:04:59.005Z", "modified": "2026-08-21T13:04:59.194Z"}, {"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": "658dcf32f8274f2caf86feccdd64ae49", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/658dcf32f8274f2caf86feccdd64ae49.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/658dcf32f8274f2caf86feccdd64ae49"}}, "title": "The Influence of Domain Permutations of an Albumin-Binding Domain-Fused HER2-Targeting Affibody-Based Drug Conjugate on Tumor Cell Proliferation and Therapy Efficacy.", "authors": [{"family": "Yin", "given": "Wen", "initials": "W"}, {"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Oroujeni", "given": "Maryam", "initials": "M", "orcid": "0000-0003-2660-9837", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bdd7a76401c42b4bbe8b11cfdb83212.json"}}, {"family": "Zhang", "given": "Jie", "initials": "J", "orcid": "0000-0002-4472-3468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b392e01b09d47e28f284d6f45e5bd93.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Vorontsova", "given": "Olga", "initials": "O"}, {"family": "Vtorushin", "given": "Sergey V", "initials": "SV"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.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": "2021-11-21", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "13", "issue": "11", "issn-l": null}, "abstract": "Human epidermal growth factor receptor 2 (HER2) is a clinically validated target for breast cancer therapy. Previously, a drug-fused HER2-targeting affinity protein construct successfully extended the survival of mice bearing HER2-expressing xenografts. The aim of this study was to evaluate the influence of the number and positioning of the protein domains in the drug conjugate. Seven HER2-targeting affibody-based constructs, including one or two affibody molecules (Z) with or without an albumin-binding domain (ABD), namely Z, Z-ABD, ABD-Z, Z-Z, Z-Z-ABD, Z-ABD-Z, and ABD-Z-Z, were evaluated on their effects on cell growth, in vivo targeting, and biodistribution. The biodistribution study demonstrated that the monomeric constructs had longer blood retention and lower hepatic uptake than the dimeric ones. A dimeric construct, specifically ABD-Z-Z, could stimulate the proliferation of HER2 expressing SKOV-3 cells in vitro and the growth of tumors in vivo, whereas the monomeric construct Z-ABD could not. These two constructs demonstrated a therapeutic effect when coupled to mcDM1; however, the effect was more pronounced for the non-stimulating Z-ABD. The median survival of the mice treated with Z-ABD-mcDM1 was 63 days compared to the 37 days for those treated with ABD-Z-Z-mcDM1 or for the control animals. Domain permutation of an ABD-fused HER2-targeting affibody-based drug conjugate significantly influences tumor cell proliferation and therapy efficacy. The monomeric conjugate Z-ABD is the most promising format for targeted delivery of the cytotoxic drug DM1.", "doi": "10.3390/pharmaceutics13111974", "pmid": "34834389", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8617914"}, {"db": "pii", "key": "pharmaceutics13111974"}], "notes": [], "created": "2026-08-21T13:04:54.714Z", "modified": "2026-08-21T13:04:54.844Z"}, {"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": "fe07ae0a7fad420aad6593affa247d96", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fe07ae0a7fad420aad6593affa247d96.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fe07ae0a7fad420aad6593affa247d96"}}, "title": "Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model.", "authors": [{"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"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", "orcid": "0000-0003-3425-0828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45b1c8e5447c41bbb93e61706377a0c7.json"}}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Vorontsova", "given": "Olga", "initials": "O"}, {"family": "Ding", "given": "Haozhong", "initials": "H", "orcid": "0000-0003-1093-8222", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ee6fb5a9b694c1d8a40cc41e9d16146.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.json"}}, {"family": "Tashireva", "given": "Liubov A", "initials": "LA", "orcid": "0000-0003-2061-8417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e462c38bfd8846588156097b5602341a.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": "Deyev", "given": "Sergey M", "initials": "SM", "orcid": "0000-0002-3952-0631", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb88df2aaa8a46a5957370b9258e2834.json"}}], "type": "journal article", "published": "2021-08-04", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "16", "issn-l": "2072-6694"}, "abstract": "Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2-positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2-targeting component. As the EpCAM-targeting component, we investigated the designed ankyrin repeat protein (DARPin) Ec1 fused to a truncated variant of Pseudomonas exotoxin A with reduced immunogenicity and low general toxicity (LoPE). Ec1-LoPE was radiolabeled, evaluated in ovarian cancer cells in vitro and its biodistribution and tumor-targeting properties were studied in vivo. The therapeutic efficacy of Ec1-LoPE alone and in combination with trastuzumab was studied in mice bearing EpCAM- and HER2-expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization of EpCAM and HER2 expression in the tumors. Co-treatment using Ec1-LoPE and trastuzumab was more effective at reducing tumor growth and prolonged the median survival of mice compared with mice in the control and monotherapy groups. Repeated administration of Ec1-LoPE was well tolerated without signs of hepatic or kidney toxicity. Co-treatment with trastuzumab and Ec1-LoPE might be a potential therapeutic strategy for HER2- and EpCAM-positive OC.", "doi": "10.3390/cancers13163939", "pmid": "34439094", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8393281"}, {"db": "pii", "key": "cancers13163939"}], "notes": [], "created": "2026-08-21T13:01:44.880Z", "modified": "2026-08-21T13:01:45.042Z"}, {"entity": "publication", "iuid": "f34c53feced64382a61689e6e503325f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f34c53feced64382a61689e6e503325f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f34c53feced64382a61689e6e503325f"}}, "title": "Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1.", "authors": [{"family": "Deyev", "given": "Sergey M", "initials": "SM", "orcid": "0000-0002-3952-0631", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb88df2aaa8a46a5957370b9258e2834.json"}}, {"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"family": "Liu", "given": "Yongsheng", "initials": "Y", "orcid": "0000-0001-5871-5779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a53363bbcb5b414681ee46ac22b65230.json"}}, {"family": "Schulga", "given": "Alexey", "initials": "A", "orcid": "0000-0003-3425-0828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45b1c8e5447c41bbb93e61706377a0c7.json"}}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Garousi", "given": "Javad", "initials": "J"}, {"family": "Rinne", "given": "Sara S", "initials": "SS", "orcid": "0000-0003-2141-3982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3aea3edd98b441c98bb527b1e0c911f5.json"}}, {"family": "Larkina", "given": "Maria", "initials": "M", "orcid": "0000-0003-1176-2441", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/557c8a9c8b2142a7a88d6211335d24e4.json"}}, {"family": "Ding", "given": "Haozhong", "initials": "H", "orcid": "0000-0003-1093-8222", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ee6fb5a9b694c1d8a40cc41e9d16146.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.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": "2021-07-17", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "14", "issn-l": "2072-6694"}, "abstract": "The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40-60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an N- or C-terminal cysteine, were produced, site-specifically conjugated to a DOTA chelator and labeled with cobalt-57, gallium-68 or indium-111. Site-specific radioiodination was performed using ((4-hydroxyphenyl)-ethyl)maleimide (HPEM). Biodistribution of eight radiolabeled Ec1-probes was measured in nude mice bearing PCa DU145 xenografts. In all cases, positioning of a label at the C-terminus provided the best tumor-to-organ ratios. The non-residualizing [125I]I-HPEM label provided the highest tumor-to-muscle and tumor-to-bone ratios and is more suitable for EpCAM imaging in early-stage PCa. Among the radiometals, indium-111 provided the highest tumor-to-blood, tumor-to-lung and tumor-to-liver ratios and could be used at late-stage PCa. In conclusion, label position and composition are important for the DARPin Ec1.", "doi": "10.3390/cancers13143589", "pmid": "34298801", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8304184"}, {"db": "pii", "key": "cancers13143589"}], "notes": [], "created": "2026-08-21T13:01:42.532Z", "modified": "2026-08-21T13:01:42.881Z"}, {"entity": "publication", "iuid": "ab67eb7a966e4796b3cb5750aa00c79b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ab67eb7a966e4796b3cb5750aa00c79b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ab67eb7a966e4796b3cb5750aa00c79b"}}, "title": "Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1.", "authors": [{"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Bezverkhniaia", "given": "Ekaterina", "initials": "E", "orcid": "0000-0001-7699-5719", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/211d24252bc84d43aed1d7ed4c3d3238.json"}}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Schulga", "given": "Alexey", "initials": "A", "orcid": "0000-0003-3425-0828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45b1c8e5447c41bbb93e61706377a0c7.json"}}, {"family": "Garousi", "given": "Javad", "initials": "J", "orcid": "0000-0002-7224-6304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e103143bca5f4a5791c496ed36351132.json"}}, {"family": "Vorontsova", "given": "Olga", "initials": "O"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Deyev", "given": "Sergey", "initials": "S", "orcid": "0000-0002-3952-0631", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb88df2aaa8a46a5957370b9258e2834.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}], "type": "journal article", "published": "2020-10-14", "journal": {"title": "Molecules", "issn": "1420-3049", "volume": "25", "issue": "20", "issn-l": "1420-3049"}, "abstract": "Efficient treatment of disseminated triple-negative breast cancer (TNBC) remains an unmet clinical need. The epithelial cell adhesion molecule (EpCAM) is often overexpressed on the surface of TNBC cells, which makes EpCAM a potential therapeutic target. Radionuclide molecular imaging of EpCAM expression might permit selection of patients for EpCAM-targeting therapies. In this study, we evaluated a scaffold protein, designed ankyrin repeat protein (DARPin) Ec1, for imaging of EpCAM in TNBC. DARPin Ec1 was labeled with a non-residualizing [125I]I-para-iodobenzoate (PIB) label and a residualizing [99mTc]Tc(CO)3 label. Both imaging probes retained high binding specificity and affinity to EpCAM-expressing MDA-MB-468 TNBC cells after labeling. Internalization studies showed that Ec1 was retained on the surface of MDA-MB-468 cells to a high degree up to 24 h. Biodistribution in Balb/c nu/nu mice bearing MDA-MB-468 xenografts demonstrated specific uptake of both [125I]I-PIB-Ec1 and [99mTc]Tc(CO)3-Ec1 in TNBC tumors. [125I]I-PIB-Ec1 had appreciably lower uptake in normal organs compared with [99mTc]Tc(CO)3-Ec1, which resulted in significantly (p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by micro-Single-Photon Emission Computed Tomography/Computed Tomography (microSPECT/CT) imaging. In conclusion, an indirectly radioiodinated Ec1 is the preferable probe for imaging of EpCAM in TNBC.", "doi": "10.3390/molecules25204719", "pmid": "33066684", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7587533"}, {"db": "pii", "key": "molecules25204719"}], "notes": [], "created": "2026-08-21T13:04:24.418Z", "modified": "2026-08-21T13:04:24.508Z"}, {"entity": "publication", "iuid": "05b37e02f1c34796981e86fefcfaf18b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/05b37e02f1c34796981e86fefcfaf18b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/05b37e02f1c34796981e86fefcfaf18b"}}, "title": "Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1.", "authors": [{"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"family": "Schulga", "given": "Alexey", "initials": "A", "orcid": "0000-0003-3425-0828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45b1c8e5447c41bbb93e61706377a0c7.json"}}, {"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Garousi", "given": "Javad", "initials": "J", "orcid": "0000-0002-7224-6304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e103143bca5f4a5791c496ed36351132.json"}}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"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", "initials": "S"}], "type": "journal article", "published": "2020-05-07", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "21", "issue": "9", "issn-l": null}, "abstract": "Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%-75% of ovarian carcinomas (OC). EpCAM might be used as a target for a treatment of disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 is a small (18 kDa) protein, which binds to EpCAM with subnanomolar affinity. We tested a hypothesis that Ec1 labeled with a non-residualizing label might serve as a companion imaging diagnostic for stratification of patients for EpCAM-targeting therapy. Ec1 was labeled with 125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [125I]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [125I]I-PIB-Ec1 were studied in Balb/c nu/nu mice bearing SKOV-3 and OVCAR-3 xenografts. EpCAM-negative Ramos lymphoma xenografts served as specificity control. Binding of [125I]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [125I]I-PIB-Ec1 by OC cells confirmed utility of non-residualizing label for in vivo imaging. [125I]I-PIB-Ec1 provided 6 h after injection tumor-to-blood ratios of 30 \u00b1 11 and 48 \u00b1 12 for OVCAR-3 and SKOV-3 xenografts, respectively, and high contrast to other organs. Tumor targeting was highly specific. Saturation of tumor uptake at a high dose of Ec1 in SKOV-3 model provided a rationale for dose selection in further studies using therapeutic conjugates of Ec1 for targeted therapy. In conclusion, [125I]I-PIB-Ec1 is a promising agent for visualizing EpCAM expression in OC.", "doi": "10.3390/ijms21093310", "pmid": "32392820", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7246691"}, {"db": "pii", "key": "ijms21093310"}], "notes": [], "created": "2026-08-21T13:03:11.331Z", "modified": "2026-08-21T13:03:11.449Z"}, {"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": "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": "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"}]}