{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:27:42Z","timestamp":1787372862429,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["075-15-2024-536"],"award-info":[{"award-number":["075-15-2024-536"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Non-invasive radionuclide molecular imaging of epidermal growth factor receptor (EGFR) expression can guide patient stratification for EGFR-targeted therapies. The designed ankyrin repeat protein (DARPin) E01, which binds EGFR ectodomain III with sub-nanomolar affinity, is a promising scaffold for single-photon emission computed tomography (SPECT) imaging probes. In the present study, we compared site-specific radioiodination of DARPin E01 using the bifunctional prosthetic group (4-hydroxyphenyl)ethyl maleimide (HPEM) with site-unspecific radioiodination via [123I]I-para-iodobenzoate (PIB). [123I]I-HPEM was conjugated to the C-terminus of DARPin E01 via Glu-Glu-Glu-Cys ([123I]I-E01-E3C-HPEM) or Gly-Gly-Gly-Cys ([123I]I-E01-G3C-HPEM) linkers. Radiolabelling yields were 6 \u00b1 2% and 13 \u00b1 5%, respectively. Size-exclusion purification provided radiochemical purity &gt; 98%. Both HPEM conjugates retained nanomolar EGFR-binding affinity (KD: 3.2 \u00b1 0.6 and 4.8 \u00b1 0.9 nM) and demonstrated EGFR-specific tumour accumulation in A-431 xenografts. Cellular processing was characterised by rapid binding, slow internalisation, and non-residualising behaviour of all variants. Kidney uptake was lower for the site-specifically labelled variants. However, site-specific labelling evidently elevated hepatobiliary excretion and uptake in Na\/I-symporter-expressing organs compared to [123I]I-(HE)3-E01-PIB, while linker composition (E3C vs. G3C) did not significantly alter biodistribution. Site-unspecific radioiodination with [123I]I-PIB remains the preferred approach for clinical SPECT imaging of EGFR expression with DARPin E01.<\/jats:p>","DOI":"10.3390\/ijms27167438","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:10:20Z","timestamp":1787213420000},"page":"7438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Site-Specific Radioiodination of Anti-EGFR-Targeted DARPin E01 Using (4-Hydroxyphenyl)ethyl Maleimide"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-2441","authenticated-orcid":false,"given":"Mariia","family":"Larkina","sequence":"first","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Department of Pharmaceutical Analysis, Siberian State Medical University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0383-3296","authenticated-orcid":false,"given":"Gleb","family":"Yanovich","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Department of Pharmaceutical Analysis, Siberian State Medical University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5614-9603","authenticated-orcid":false,"given":"Lutfi A.","family":"Hasnowo","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Polytechnic Institute of Nuclear Technology, National Research and Innovation Agency of Indonesia, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4282-3198","authenticated-orcid":false,"given":"Ruslan","family":"Varvashenya","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Eskova","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Sharychev","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6975-2361","authenticated-orcid":false,"given":"Anastasia","family":"Prach","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-6422","authenticated-orcid":false,"given":"Evgenii","family":"Plotnikov","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Zelchan","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Department of Nuclear Medicine, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-0828","authenticated-orcid":false,"given":"Alexey","family":"Schulga","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-376X","authenticated-orcid":false,"given":"Elena","family":"Konovalova","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7931-519X","authenticated-orcid":false,"given":"Rustam H.","family":"Ziganshin","sequence":"additional","affiliation":[{"name":"Collective Use Center \u201cBioorganic\u201d, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-7945","authenticated-orcid":false,"given":"Mikhail","family":"Belousov","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Department of Pharmaceutical Analysis, Siberian State Medical University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6122-1734","authenticated-orcid":false,"given":"Vladimir","family":"Tolmachev","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3952-0631","authenticated-orcid":false,"given":"Sergey M.","family":"Deyev","sequence":"additional","affiliation":[{"name":"Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia"},{"name":"Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zahavi, D., and Weiner, L. (2020). Monoclonal Antibodies in Cancer Therapy. Antibodies, 9.","DOI":"10.3390\/antib9030034"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yu, J., Fang, T., Yun, C., Liu, X., and Cai, X. (2022). Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.847835"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/sj.bjc.6603619","article-title":"A Simple and Reproducible Scoring System for EGFR in Colorectal Cancer: Application to Prognosis and Prediction of Response to Preoperative Brachytherapy","volume":"96","author":"Zlobec","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41273","DOI":"10.1074\/jbc.M111.293266","article-title":"Bispecific Designed Ankyrin Repeat Proteins (DARPins) Targeting Epidermal Growth Factor Receptor Inhibit A431 Cell Proliferation and Receptor Recycling","volume":"286","author":"Boersma","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1200\/JCO.2009.27.4860","article-title":"Randomized, Phase III Trial of Panitumumab with Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) versus FOLFOX4 Alone as First-Line Treatment in Patients with Previously Untreated Metastatic Colorectal Cancer: The PRIME Study","volume":"28","author":"Douillard","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S1470-2045(15)00021-2","article-title":"Necitumumab plus Gemcitabine and Cisplatin versus Gemcitabine and Cisplatin Alone as First-Line Therapy in Patients with Stage IV Squamous Non-Small-Cell Lung Cancer (SQUIRE): An Open-Label, Randomised, Controlled Phase 3 Trial","volume":"16","author":"Thatcher","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_7","first-page":"118087","article-title":"A clinical review on third and fourth generation EGFR tyrosine kinase inhibitors for the treatment of non-small cell lung cancer","volume":"117","author":"Gawli","year":"2025","journal-title":"Bioorg. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114390","DOI":"10.1016\/j.biopha.2023.114390","article-title":"Near-infrared photoimmunotherapy (NIR-PIT) of bone metastases","volume":"160","author":"Inagaki","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jtho.2017.12.001","article-title":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: Guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology","volume":"13","author":"Lindeman","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1136\/jclinpath-2012-201194","article-title":"EGFR mutation testing in lung cancer: A review of available methods and their use for analysis of tumour tissue and cytology samples","volume":"66","author":"Ellison","year":"2013","journal-title":"J. Clin. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1470-2045(11)70318-7","article-title":"EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: Analysis of data from the phase 3 FLEX study","volume":"13","author":"Pirker","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cllc.2021.10.002","article-title":"EGFR High Copy Number Together With High EGFR Protein Expression Predicts Improved Outcome for Cetuximab-based Therapy in Squamous Cell Lung Cancer: Analysis From SWOG S0819, a Phase III Trial of Chemotherapy With or Without Cetuximab in Advanced NSCLC","volume":"23","author":"Hirsch","year":"2022","journal-title":"Clin. Lung Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eaan8840","DOI":"10.1126\/scitranslmed.aan8840","article-title":"A PET Imaging Approach for Determining EGFR Mutation Status for Improved Lung Cancer Patient Management","volume":"10","author":"Sun","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cri\u0219an, G., Moldovean-Cioroianu, N.S., Timaru, D.-G., Andrie\u0219, G., C\u0103inap, C., and Chi\u0219, V. (2022). Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095023"},{"key":"ref_15","first-page":"1209","article-title":"Comparison of Tumor-targeting Properties of Directly and Indirectly Radioiodinated Designed Ankyrin Repeat Protein (DARPin) G3 Variants for Molecular Imaging of HER2","volume":"54","author":"Vorobyeva","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1136\/jcp.2005.028373","article-title":"Pitfalls in Immunohistochemical Assessment of EGFR Expression in Soft Tissue Sarcomas","volume":"59","author":"Kersting","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1158\/1535-7163.MCT-06-0809","article-title":"Progressive Loss of Epidermal Growth Factor Receptor in a Subpopulation of Breast Cancers: Implications in Target-Directed Therapeutics","volume":"6","author":"Choong","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.lungcan.2023.01.014","article-title":"Liquid biopsy-based decision support algorithms for diagnosis and subtyping of lung cancer","volume":"178","author":"Visser","year":"2023","journal-title":"Lung Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Desai, A., V\u00e1zquez, T.A., Arce, K.M., Corassa, M., Mack, P.C., Gray, J.E., and Pellini, B. (2024). ctDNA for the Evaluation and Management of EGFR-Mutant Non-Small Cell Lung Cancer. Cancers, 16.","DOI":"10.3390\/cancers16050940"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s00259-019-04555-6","article-title":"[89Zr]Zr-cetuximab PET\/CT as biomarker for cetuximab monotherapy in patients with RAS wild-type advanced colorectal cancer","volume":"47","author":"Elias","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.18632\/oncotarget.13910","article-title":"Quantitative Assessment of Zirconium-89 Labeled Cetuximab Using PET\/CT Imaging in Patients with Advanced Head and Neck Cancer: A Theragnostic Approach","volume":"8","author":"Even","year":"2017","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.7150\/thno.86770","article-title":"Phase I Clinical Evaluation of 99mTc-Labeled Affibody Molecule for Imaging HER2 Expression in Breast Cancer","volume":"13","author":"Bragina","year":"2023","journal-title":"Theranostics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1097\/CCO.0000000000000598","article-title":"Beyond tissue biopsy: A diagnostic framework to address tumor heterogeneity in lung cancer","volume":"32","author":"Prosch","year":"2020","journal-title":"Curr. Opin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s41181-026-00446-y","article-title":"Radionuclide-based pharmaceuticals for breast cancer imaging: State of the art","volume":"11","author":"Seimbille","year":"2026","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.radonc.2016.11.020","article-title":"PET Imaging of Zirconium-89 Labelled Cetuximab: A Phase I Trial in Patients with Head and Neck and Lung Cancer","volume":"122","author":"Even","year":"2017","journal-title":"Radiother. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.2967\/jnumed.113.123612","article-title":"Imaging of Epidermal Growth Factor Receptor Expression in Head and Neck Cancer with SPECT\/CT and 111In-Labeled Cetuximab-F(ab\u2032)2","volume":"54","author":"Hoeben","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.nucmedbio.2014.10.009","article-title":"MicroPET\/CT Imaging of Patient-Derived Pancreatic Cancer Xenografts Implanted Subcutaneously or Orthotopically in NOD-Scid Mice Using (64Cu)-NOTA-Panitumumab F(ab\u2032)2 Fragments","volume":"42","author":"Boyle","year":"2015","journal-title":"Nucl. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2967\/jnumed.118.216069","article-title":"Affibody-Based PET Imaging to Guide EGFR-Targeted Cancer Therapy in Head and Neck Squamous Cell Cancer Models","volume":"60","author":"Burley","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3892\/ijo.2016.3369","article-title":"PET Imaging of Epidermal Growth Factor Receptor Expression in Tumours Using 89Zr-Labelled ZEGFR:2377 Affibody Molecules","volume":"48","author":"Garousi","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1021\/acs.molpharmaceut.6b00538","article-title":"64Cu-Labeled Gp2 Domain for PET Imaging of Epidermal Growth Factor Receptor","volume":"13","author":"Kruziki","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1096\/fj.05-4058com","article-title":"Identification and Characterization of a Novel Peptide Ligand of Epidermal Growth Factor Receptor for Targeted Delivery of Therapeutics","volume":"19","author":"Li","year":"2005","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s00726-018-2616-5","article-title":"Exploring Pitfalls of 64Cu-Labeled EGFR-Targeting Peptide GE11 as a Potential PET Tracer","volume":"50","author":"Striese","year":"2018","journal-title":"Amino Acids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s00726-018-2571-1","article-title":"Influence of Composition of Cysteine-Containing Peptide-Based Chelators on Biodistribution of 99mTc-Labeled Anti-EGFR Affibody Molecules","volume":"50","author":"Oroujeni","year":"2018","journal-title":"Amino Acids"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1007\/s10967-023-09048-3","article-title":"The Development of Cyclotron-Based Radiopharmaceuticals: A Comprehensive Review of 64Cu and 123I-Radiolabeled Urea-Based Small Molecule PSMA Ligands","volume":"332","author":"Hasnowo","year":"2023","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Chang, M.-C., Peng, C.-L., Chen, C.-T., Shih, Y.-H., Chen, J.-H., Tai, Y.-J., and Chiang, Y.-C. (2024). Iodine-123Metaiodobenzylguanidine (I-123MIBG) in Clinical Applications: A Comprehensive Review. Pharmaceuticals, 17.","DOI":"10.3390\/ph17121563"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vorobyeva, A., Schulga, A., Rinne, S.S., G\u00fcnther, T., Orlova, A., Deyev, S., and Tolmachev, V. (2019). Indirect Radioiodination of DARPin G3 Using N-Succinimidyl-para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123047"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1186\/s12951-025-03868-z","article-title":"A high-affinity CEA-targeted nanobody for 68Ga PET imaging and 177Lu-based radio-isotope therapy: Preclinical and first-in-human evaluation","volume":"23","author":"Zhang","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.jmb.2008.07.085","article-title":"Efficient Selection of DARPins with Sub-Nanomolar Affinities Using SRP Phage Display","volume":"382","author":"Steiner","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Karsten, L., Janson, N., Le Joncour, V., Alam, S., M\u00fcller, B., Ramanathan, J.T., Laakkonen, P., Sewald, N., and M\u00fcller, K.M. (2022). Bivalent EGFR-Targeting DARPin-MMAE Conjugates. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052468"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Larkina, M., Yanovich, G., Hasnowo, L.A., Varvashenya, R., Eskova, D., Sharishev, I., Plotnikov, E., Zelchan, R., Schulga, A., and Konovalova, E. (2025). Comparative Preclinical Evaluation of the Tumor-Targeting Properties of Radioiodine and Technetium-Labeled Designed Ankyrin Repeat Proteins for Imaging of Epidermal Growth Factor Receptor Expression in Malignant Tumors. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110609"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"942","DOI":"10.2967\/jnumed.109.071290","article-title":"Preparation, biological evaluation, and pharmacokinetics of the human anti-HER1 monoclonal antibody panitumumab labeled with 86Y for quantitative PET of carcinoma","volume":"51","author":"Nayak","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ijbiomac.2019.12.147","article-title":"Effect of a Radiolabel Biochemical Nature on Tumor-Targeting Properties of EpCAM-Binding Engineered Scaffold Protein DARPin Ec1","volume":"145","author":"Deyev","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Deyev, S.M., Xu, T., Liu, Y., Schulga, A., Konovalova, E., Garousi, J., Rinne, S.S., Larkina, M., Ding, H., and Gr\u00e4slund, T. (2021). Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of EpCAM Expression in Prostate Cancer Model Using the DARPin Ec1. Cancers, 13.","DOI":"10.3390\/cancers13143589"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.nucmedbio.2014.07.005","article-title":"N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: Influence of isomeric substitution on radiolabeling and target cell residualization","volume":"41","author":"Choi","year":"2014","journal-title":"Nucl. Med. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dewulf, J., Adhikari, K., Vangestel, C., Wyngaert, T.V.D., and Elvas, F. (2020). Development of Antibody Immuno-PET\/SPECT Radiopharmaceuticals for Imaging of Oncological Disorders\u2014An Update. Cancers, 12.","DOI":"10.3390\/cancers12071868"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2967\/jnumed.117.197202","article-title":"Radionuclide tumor targeting using ADAPT scaffold proteins: Aspects of label positioning and residualizing properties of the label","volume":"59","author":"Lindbo","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1021\/acs.molpharmaceut.5c01498","article-title":"The Use of Glycine-Containing Peptide-Based Chelators for Labeling with 99mTc Improves the Imaging Properties of EpCAM-Targeting Designed Ankyrin Repeat Ec1","volume":"23","author":"Deyev","year":"2026","journal-title":"Mol. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S1040-8428(00)00134-7","article-title":"Development of ABX-EGF, a Fully Human Anti-EGF Receptor Monoclonal Antibody, for Cancer Therapy","volume":"38","author":"Yang","year":"2001","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1158\/1078-0432.CCR-03-0521","article-title":"Resistance to Tyrosine Kinase Inhibition by Mutant Epidermal Growth Factor Receptor Variant III Contributes to the Neoplastic Phenotype of Glioblastoma Multiforme","volume":"10","author":"Learn","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s00259-008-1003-y","article-title":"Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules","volume":"36","author":"Tolmachev","year":"2009","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1021\/acs.molpharmaceut.6b00089","article-title":"Increasing the Net Negative Charge by Replacement of DOTA Chelator with DOTAGA Improves the Biodistribution of Radiolabeled Second-Generation Synthetic Affibody Molecules","volume":"13","author":"Westerlund","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9405","DOI":"10.1038\/s41598-019-45795-8","article-title":"Optimal Composition and Position of Histidine-Containing Tags Improves Biodistribution of 99mTc-Labeled DARPin G3","volume":"9","author":"Vorobyeva","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s00259-014-2940-2","article-title":"Development of the Designed Ankyrin Repeat Protein (DARPin) G3 for HER2 Molecular Imaging","volume":"42","author":"Goldstein","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.2967\/jnumed.110.075101","article-title":"Renal toxicity of radiolabeled peptides and antibody fragments: Mechanisms, impact on radionuclide therapy, and strategies for prevention","volume":"51","author":"Vegt","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Presser, A., Lainer, G., Kretschmer, N., Schuehly, W., Saf, R., Kaiser, M., and Kalt, M.M. (2018). Synthesis of Jacaranone-Derived Nitrogenous Cyclohexadienones and Their Antiproliferative and Antiprotozoal Activities. Molecules, 23.","DOI":"10.3390\/molecules23112902"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7438\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:15:15Z","timestamp":1787372115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":55,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167438"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167438","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}