Published in:
01-10-2011 | Research Article
PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel 18F-Labeled Biotin Derivative
Authors:
Takashi Kudo, Masashi Ueda, Hiroaki Konishi, Hidekazu Kawashima, Yuji Kuge, Takahiro Mukai, Azusa Miyano, Shotaro Tanaka, Shinae Kizaka-Kondoh, Masahiro Hiraoka, Hideo Saji
Published in:
Molecular Imaging and Biology
|
Issue 5/2011
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Abstract
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-1α 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-1α-positive areas.
Conclusion
Pretargeting with POS and 18F-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.