PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel 18F-Labeled Biotin Derivative

• Published in: Molecular imaging and biology 2011-10, Vol.13 (5), p.1003-1010
• Main Authors: Kudo, Takashi, Ueda, Masashi, Konishi, Hiroaki, Kawashima, Hidekazu, Kuge, Yuji, Mukai, Takahiro, Miyano, Azusa, Tanaka, Shotaro, Kizaka-Kondoh, Shinae, Hiraoka, Masahiro, Saji, Hideo
• Format: Article
• Language: English
• Subjects: Animals; Biotin - metabolism; Cell Line, Tumor; Fluorine Radioisotopes - metabolism; Hypoxia-Inducible Factor 1 - metabolism; Imaging; Immunohistochemistry; Medicine; Medicine & Public Health; Mice; Oxygen - metabolism; Positron-Emission Tomography; Radiology; Research Article; Streptavidin
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-010-0418-6

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