PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel 18F-labeled biotin derivative Takashi Kudo,1 Masashi Ueda,1,2 Hiroaki Konishi,1 Hidekazu Kawashima,1,3

Takashi Kudo, Masashi Ueda, Hiroaki Konishi, Hidekazu Kawashima, Yuji Kuge, Takahiro Mukai, Azusa Miyano, Shotaro Tanaka, Shinae Kizaka-Kondoh, Masahiro Hiraoka, Hideo Saji

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)1003-1010
Number of pages8
JournalMolecular Imaging and Biology
Volume13
Issue number5
DOIs
Publication statusPublished - Oct 1 2011
Externally publishedYes

Keywords

  • F-labeled biotin derivative
  • Hypoxia-inducible factor-1 (HIF-1)
  • Oxygen-dependent degradation domain (ODD)
  • Pretargeting
  • Tumor hypoxia

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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