title: PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel 18F-labeled biotin derivative.
abstract: 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.
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Konishi
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kawashima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Azusa
authors.initials: A
authors.lastname: Miyano
authors.forename: Shotaro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D001710:Biotin / Q000378:metabolism*; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019809:Streptavidin
chemical_list: D005462:Fluorine Radioisotopes; D051793:Hypoxia-Inducible Factor 1; D001710:Biotin; D019809:Streptavidin; D010100:Oxygen