{"entity": "publication", "iuid": "0a26121eb2c0440fb0cd172fd0ec08f8", "timestamp": "2026-08-29T04:16:07.190Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0a26121eb2c0440fb0cd172fd0ec08f8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0a26121eb2c0440fb0cd172fd0ec08f8"}}, "title": "Comparison of tumor\u2011targeting properties of directly and indirectly radioiodinated designed ankyrin repeat protein (DARPin) G3 variants for molecular imaging of HER2.", "authors": [{"family": "Vorobyeva", "given": "Anzhelika", "initials": "A"}, {"family": "S\u0441hulga", "given": "Alexey", "initials": "A"}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "G\u00fcler", "given": "Rezan", "initials": "R"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Garousi", "given": "Javad", "initials": "J"}, {"family": "Rinne", "given": "Sara", "initials": "S"}, {"family": "L\u00f6fblom", "given": "John", "initials": "J"}, {"family": "Orlova", "given": "Anna", "initials": "A"}, {"family": "Deyev", "given": "Sergey", "initials": "S"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}], "type": "comparative study", "published": "2019-04-00", "journal": {"title": "Int. J. Oncol.", "issn": "1791-2423", "volume": "54", "issue": "4", "pages": "1209-1220", "issn-l": "1791-2423"}, "abstract": "Evaluation of human epidermal growth factor receptor 2 (HER2) expression levels in breast and gastroesophageal cancer is used for the stratification of patients for HER2\u2011targeting therapies. The use of radionuclide molecular imaging may facilitate such evaluation in a non\u2011invasive way. Designed ankyrin repeat proteins (DARPins) are engineered scaffold proteins with high potential as probes for radionuclide molecular imaging. DARPin G3 binds with high affinity to HER2 and may be used to visualize this important therapeutic target. Studies on other engineered scaffold proteins have demonstrated that selection of the optimal labeling approach improves the sensitivity and specificity of radionuclide imaging. The present study compared two methods of labeling G3, direct and indirect radioiodination, to select an approach providing the best imaging contrast. G3\u2011H6 was labeled with iodine\u2011124, iodine\u2011125 and iodine\u2011131 using a direct method. A novel construct bearing a C\u2011terminal cysteine, G3\u2011GGGC, was site\u2011specifically labeled using [125I]I\u2011iodo\u2011[(4\u2011hydroxyphenyl)ethyl]maleimide (HPEM). The two radiolabeled G3 variants preserved binding specificity and high affinity to HER2\u2011expressing cells. The specificity of tumor targeting in vivo was demonstrated. Biodistribution comparison of [131I]I\u2011G3\u2011H6 and [125I]I\u2011HPEM\u2011G3\u2011GGGC in mice, bearing HER2\u2011expressing SKOV3 xenografts, demonstrated an appreciable contribution of hepatobiliary excretion to the clearance of [125I]I\u2011HPEM\u2011G3\u2011GGGC and a decreased tumor uptake compared to [131I]I\u2011G3\u2011H6. The direct label provided higher tumor\u2011to\u2011blood and tumor\u2011to\u2011organ ratios compared with the indirect label at 4 h post\u2011injection. The feasibility of high contrast PET/CT imaging of HER2 expression in SKOV3 xenografts in mice using [124I]I\u2011G3\u2011H6 was demonstrated. In conclusion, direct radioiodination is the preferable approach for labeling DARPin G3 with iodine\u2011123 and iodine\u2011124 for clinical single photon emission computed tomography and positron emission tomography imaging.", "doi": "10.3892/ijo.2019.4712", "pmid": "30968147", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6411343"}], "notes": [], "created": "2026-08-21T13:05:41.544Z", "modified": "2026-08-21T13:05:41.557Z"}