PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel [18]F-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 < 0.05), and most of the area showing [18]F-FBB accumulation corresponded to HIF-1α-positive areas. <Conclusion> : Pretargeting with POS and [18]F-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.
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