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タイトル: Development of an oxygen-sensitive degradable peptide probe for the imaging of hypoxia-inducible factor-1-active regions in tumors.
著者: Ueda, Masashi
Ogawa, Kei
Miyano, Azusa
Ono, Masahiro  kyouindb  KAKEN_id
Kizaka-Kondoh, Shinae
Saji, Hideo
著者名の別形: 上田, 真史
佐治, 英郎
キーワード: Tumor hypoxia
Hypoxia-inducible factor-1
Oxygen-dependent degradation
Peptide
Nuclear medical imaging
発行日: 21-May-2013
出版者: Springer US
誌名: Molecular imaging and biology
巻: 15
号: 6
開始ページ: 713
終了ページ: 721
抄録: [Purpose]We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors. [Procedures]We synthesized the peptide probes that contain or lack an essential sequence of the oxygen-dependent degradation of HIF-1α in proteasomes ([123/125]I-DKOP30 or [125]I-mDKOP, respectively). The degradation of probes was evaluated in vitro using cell lysates containing proteasomes. In vivo biodistribution study, planar imaging, autoradiography, and comparison between probe accumulation and HIF-1 transcriptional activity were also performed. [Results]The [125]I-DKOP30 underwent degradation in a proteasome-dependent manner, while [125]I-mDKOP was not degraded. Biodistribution analysis showed [125]I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of [125]I-DKOP30 coincided with the HIF-1α-positive hypoxic regions. Tumoral accumulation of 125I-DKOP30 was significantly correlated with HIF-1-dependent luciferase bioluminescence, while that of [125]I-mDKOP was not. [Conclusion] [123]I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.
著作権等: The final publication is available at Springer via http://dx.doi.org/10.1007/s11307-013-0647-6
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/2433/196858
DOI(出版社版): 10.1007/s11307-013-0647-6
PubMed ID: 23689986
出現コレクション:学術雑誌掲載論文等

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