PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel 18F-Labeled Biotin Derivative
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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.
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.
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.
Pretargeting with POS and 18F-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.
Key WordsTumor hypoxia Hypoxia-inducible factor-1 (HIF-1) Oxygen-dependent degradation domain (ODD) Pretargeting 18F-labeled biotin derivative
We are grateful to Hiroyuki Kimura, Kenji Tomatsu, and Yu Ogawa for preparation of 18F-SFB, and Kei Ogawa for skilled technical assistance.
This study was supported in part by Health Labour Sciences Research Grant for Research on Advanced Medical Technology from the Ministry of Health, Labour and Welfare of Japan; “R&D of Molecular Imaging Equipment for Malignant Tumor Therapy Support” by the New Energy and Industrial Technology Development Organization (NEDO), Japan; and a Grant-in-Aid for Exploratory Research (17659010) and a Grant-in-Aid for Young Scientists (B) (21791187) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Conflict of interest
The authors have no conflict of interest.
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