Evaluation of an Affibody-Based Binder for Imaging of Immune Check-Point Molecule B7-H3
Maryam Oroujeni,
Ekaterina A. Bezverkhniaia,
Tianqi Xu,
Yongsheng Liu,
Evgenii V. Plotnikov,
Ida Karlberg,
Eva Ryer,
Anna Orlova,
Vladimir Tolmachev,
Fredrik Y. Frejd
Affiliations
Maryam Oroujeni
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Ekaterina A. Bezverkhniaia
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia
Tianqi Xu
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Yongsheng Liu
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Evgenii V. Plotnikov
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia
Ida Karlberg
Affibody AB, 171 65 Solna, Sweden
Eva Ryer
Affibody AB, 171 65 Solna, Sweden
Anna Orlova
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia
Vladimir Tolmachev
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Fredrik Y. Frejd
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
Radionuclide molecular imaging could provide an accurate assessment of the expression of molecular targets in disseminated cancers enabling stratification of patients for specific therapies. B7-H3 (CD276) is a transmembrane protein belonging to the B7 superfamily. This protein is overexpressed in different types of human malignancies and such upregulation is generally associated with a poor clinical prognosis. In this study, targeting properties of an Affibody-based probe, AC12, containing a -GGGC amino acid sequence as a chelator (designated as AC12-GGGC) labelled with technetium-99m (99mTc) were evaluated for imaging of B7-H3-expressing tumours. AC12-GGGC was efficiently labelled with 99mTc. [99mTc]Tc-AC12-GGGC bound specifically to B7-H3 expressing cells in vitro with affinities in nanomolar range. In mice bearing B7-H3-expressing xenografts, [99mTc]Tc-AC12-GGGC showed tumour uptake of 2.1 ± 0.5 %ID/g at 2 h after injection. Its clearance from blood, normal organs and tissues was very rapid. This new targeting agent, [99mTc]Tc-AC12-GGGC, provided high tumour-to-blood ratio already at 2 h (8.2 ± 1.9), which increased to 11.0 ± 0.5 at 4 h after injection. Significantly (p 99mTc]Tc-AC12-GGGC could be a promising candidate for further development.
