Evaluation of an Affibody-Based Binder for Imaging of Immune Check-Point Molecule B7-H3

• Main Authors: Maryam Oroujeni (Author), Ekaterina A. Bezverkhniaia (Author), Tianqi Xu (Author), Yongsheng Liu (Author), Evgenii V. Plotnikov (Author), Ida Karlberg (Author), Eva Ryer (Author), Anna Orlova (Author), Vladimir Tolmachev (Author), Fredrik Y. Frejd (Author)
• Format: Book
• Published: MDPI AG, 2022-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 (<i>p</i> < 0.05) higher tumour-to-liver and higher tumour-to-bone ratios at 2 h in comparison with 4 h after injection were observed. Thus, [^99mTc]Tc-AC12-GGGC could be a promising candidate for further development.

Item Description

10.3390/pharmaceutics14091780
1999-4923