PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel 18F-labeled biotin derivative

Mol Imaging Biol. 2011 Oct;13(5):1003-10. doi: 10.1007/s11307-010-0418-6.

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-(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.

Conclusion: Pretargeting with POS and (18)F-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotin / metabolism*
  • Cell Line, Tumor
  • Fluorine Radioisotopes / metabolism*
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Immunohistochemistry
  • Mice
  • Oxygen / metabolism*
  • Positron-Emission Tomography*
  • Streptavidin

Substances

  • Fluorine Radioisotopes
  • Hypoxia-Inducible Factor 1
  • Biotin
  • Streptavidin
  • Oxygen