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

• 上田, 真史

• 佐治, 英郎

• Kuge, Yuji

• Mukai, Takahiro

• Tanaka, Shotaro

• Konishi, Hiroaki

• Miyano, Azusa

• Ono, Masahiro

• Kizaka-Kondoh, Shinae

• Hiraoka, Masahiro

• Saji, Hideo

抄録

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-(123)I-iodobenzoyl)norbiotinamide ((123)I-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 (123)I-IBB for rapid imaging of HIF-1-active tumours. METHODS: Tumour-implanted mice were pretargeted with POS. After 24 h, (125)I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between (125)I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of (125)I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1alpha immunohistochemistry. RESULTS: (125)I-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 (125)I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of (125)I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of (125)I-IBB was heterogeneous and was significantly correlated with HIF-1alpha-positive regions (R=0.58, p<0.0001). CONCLUSION: POS pretargeting with (123)I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours.

収録刊行物

• European journal of nuclear medicine and molecular imaging

  European journal of nuclear medicine and molecular imaging 37 (8), 1566-1574, 2010-08

  Springer

キーワード

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

詳細情報

• CRID: 1050282677154709888
• NII論文ID: 120002511114
• NII書誌ID: AA1161516X
• ISSN: 16197070
• ISSN: 16197089
• HANDLE: 2433/128622
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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