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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  kyouindb  KAKEN_id
Kizaka-Kondoh, Shinae
Hiraoka, Masahiro  KAKEN_id
Saji, Hideo  kyouindb  KAKEN_id
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 Verlag
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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