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タイトル: | Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1alpha |
著者: | Ueda, Masashi Kudo, Takashi Kuge, Yuji Mukai, Takahiro Tanaka, Shotaro Konishi, Hiroaki Miyano, Azusa Ono, Masahiro https://orcid.org/0000-0002-2497-039X (unconfirmed) Kizaka-Kondoh, Shinae Hiraoka, Masahiro Saji, Hideo |
著者名の別形: | 上田, 真史 佐治, 英郎 |
キーワード: | Tumour hypoxia Hypoxia-inducible factor-1 (HIF-1) Oxygen-dependent degradation (ODD) Molecular imaging Pretargeting |
発行日: | Aug-2010 |
出版者: | Springer |
誌名: | European journal of nuclear medicine and molecular imaging |
巻: | 37 |
号: | 8 |
開始ページ: | 1566 |
終了ページ: | 1574 |
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. |
著作権等: | The original publication is available at www.springerlink.com This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/128622 |
DOI(出版社版): | 10.1007/s00259-010-1467-4 |
PubMed ID: | 20428865 |
出現コレクション: | 学術雑誌掲載論文等 |
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