TY - JOUR
T1 - Development of an oxygen-sensitive degradable peptide probe for the imaging of hypoxia-inducible factor-1-active regions in tumors
AU - Ueda, Masashi
AU - Ogawa, Kei
AU - Miyano, Azusa
AU - Ono, Masahiro
AU - Kizaka-Kondoh, Shinae
AU - Saji, Hideo
N1 - Funding Information:
Acknowledgments. The authors would like to thank Nihon Medi-Physics Co. Ltd. for providing ammonium [123I]iodide. This work was supported in part by the Research and Development Project on Molecular Probes for Detection of Biological Features on Cancer of the New Energy and Industrial Technology Development Organization (NEDO), Japan, and a Grant-in-Aid for Young Scientists (B) (KAKENHI Grant Number 23791412) from the Japan Society for the Promotion of Science.
PY - 2013/12
Y1 - 2013/12
N2 - 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 ( 123/125I-DKOP30 or 125I-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 125I-DKOP30 underwent degradation in a proteasome-dependent manner, while 125I-mDKOP was not degraded. Biodistribution analysis showed 125I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of 125I-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 125I-mDKOP was not. Conclusion: 123I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.
AB - 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 ( 123/125I-DKOP30 or 125I-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 125I-DKOP30 underwent degradation in a proteasome-dependent manner, while 125I-mDKOP was not degraded. Biodistribution analysis showed 125I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of 125I-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 125I-mDKOP was not. Conclusion: 123I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.
KW - Hypoxia-inducible factor-1
KW - Nuclear medical imaging
KW - Oxygen-dependent degradation
KW - Peptide
KW - Tumor hypoxia
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U2 - 10.1007/s11307-013-0647-6
DO - 10.1007/s11307-013-0647-6
M3 - Article
C2 - 23689986
AN - SCOPUS:84890478073
SN - 1536-1632
VL - 15
SP - 713
EP - 721
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 6
ER -
