Rapid detection of hypoxia-inducible factor-1-active tumours: Pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1α

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

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Purpose: Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-123I-iodobenzoyl)norbiotinamide (123I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and 123I-IBB for rapid imaging of HIF-1-active tumours. Methods: Tumour-implanted mice were pretargeted with POS. After 24 h, 125I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between 125I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of 125I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1α immunohistochemistry. Results: 125I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from 125I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of 125I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of 125I-IBB was heterogeneous and was significantly correlated with HIF-1α-positive regions (R=0.58, p<0.0001). Conclusion: POS pretargeting with 123I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours.

Original languageEnglish
Pages (from-to)1566-1574
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume37
Issue number8
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

Keywords

  • Hypoxia-inducible factor-1 (HIF-1)
  • Molecular imaging
  • Oxygen-dependent degradation (ODD)
  • Pretargeting
  • Tumour hypoxia

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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