Synthesis and bioevaluation of novel ^99mTc-labelled ferrioxamine B isonitrile complexes as potential bacterial...

Bacterial infections remain a significant threat to human health, necessitating the development of specific imaging agents for accurate diagnosis. Since bacteria acquire iron from hosts via ferrioxamine B siderophore, this study synthesized and evaluated novel ^99mTc-labelled ferrioxamine B isonitrile derivatives for bacterial infection SPECT imaging. The derivatives were radiolabelled with two technetium cores: [^99mTc][Tc(CO)₃]⁺, and [^99mTc]Tc⁺ cores. Among them, [^99mTc]Tc-L1 showed excellent hydrophilicity (logD = -2.69 ± 0.03), in vitro and in vivo stability (>95 % RCP), and specific binding to Staphylococcus aureus. Ex vivo studies demonstrated rapid blood clearance, high abscess uptake (1.48 ± 0.51 % ID/g at 120 min p.i.), and good target-to-background ratios (abscess/muscle = 3.63 ± 0.10 at 240 min p.i.). Molecular docking revealed strong binding to FhuD2 (ΔG = -276.824 kJ/mol). SPECT imaging in the dual-pathology model successfully distinguished bacterial infection from sterile inflammation. These results highlight [^99mTc]Tc-L1 as a promising bacteria-specific SPECT imaging agent.