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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 (Tc-99m) were evaluated for imaging of B7-H3-expressing tumours. AC12-GGGC was efficiently labelled with Tc-99m. [Tc-99m]Tc-AC12-GGGC bound specifically to B7-H3 expressing cells in vitro with affinities in nanomolar range. In mice bearing B7-H3-expressing xenografts, [Tc-99m]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, [Tc-99m]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 < 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, [Tc-99m]Tc-AC12-GGGC could be a promising candidate for further development.