PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel 18F-Labeled Biotin Derivative

Purpose We aimed to evaluate the feasibility of using streptavidin–biotin-based pretargeting for positron emission tomography (PET) imaging of hypoxia-inducible factor (HIF)-1-active tumors. Procedures We used POS, a genetically engineered form of streptavidin that selectively stabilizes in HIF-1-active cells, and (4- 18 F-fluorobenzoyl)norbiotinamide ( 18 F-FBB), a radiolabeled biotin derivative, for performing a biodistribution study and for PET imaging. The tumoral 18 F-FBB accumulation was compared to the HIF-1-dependent luciferase bioluminescence and HIF-1α immunohistochemical signal. Results 18 F-FBB accumulation was observed in POS-pretargeted tumors in mice (2.85 ± 0.55% injected dose per gram at 3 h), and clear PET images were obtained at the same time point. The tumoral 18 F-FBB accumulation positively correlated with luciferase bioluminescence ( R = 0.72, P