PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel 18F-labeled biotin derivative.
Mots clés
Abstrait
OBJECTIVE
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.
METHODS
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.
CONCLUSIONS
Pretargeting with POS and (18)F-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.
