PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel ¹⁸F-labeled biotin derivative Takashi Kudo,1 Masashi Ueda,1,2 Hiroaki Konishi,1 Hidekazu Kawashima,1,3

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- ¹⁸F-fluorobenzoyl)norbiotinamide ( ¹⁸F-FBB), a radiolabeled biotin derivative, for performing a biodistribution study and for PET imaging. The tumoral ¹⁸F-FBB accumulation was compared to the HIF-1-dependent luciferase bioluminescence and HIF-1a immunohistochemical signal. Results: ¹⁸F-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 ¹⁸F-FBB accumulation positively correlated with luciferase bioluminescence (R=0.72, P<0.05), and most of the area showing ¹⁸F-FBB accumulation corresponded to HIF-1a-positive areas. Conclusion: Pretargeting with POS and ¹⁸F-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.