Development of an Oxygen-Sensitive Degradable Peptide Probe for the Imaging of Hypoxia-Inducible Factor-1-Active Regions in Tumors

作者：Ueda Masashi; Ogawa Kei; Miyano Azusa; Ono Masahiro; Kizaka Kondoh Shinae; Saji Hideo^*

来源：Molecular Imaging and Biology, 2013, 15(6): 713-721.

DOI：10.1007/s11307-013-0647-6

• Tumor hypoxia
• Hypoxia-inducible factor-1
• Oxygen-dependent degradation
• Peptide
• Nuclear medical imaging

We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors. %26lt;br%26gt;We synthesized the peptide probes that contain or lack an essential sequence of the oxygen-dependent degradation of HIF-1 alpha in proteasomes (I-123/125-DKOP30 or I-125-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. %26lt;br%26gt;The I-125-DKOP30 underwent degradation in a proteasome-dependent manner, while I-125-mDKOP was not degraded. Biodistribution analysis showed I-125-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of I-125-DKOP30 coincided with the HIF-1 alpha-positive hypoxic regions. Tumoral accumulation of I-125-DKOP30 was significantly correlated with HIF-1-dependent luciferase bioluminescence, while that of I-125-mDKOP was not. %26lt;br%26gt;I-123-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.

• 出版日期2013-12