Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Mol Imaging Biol. 2013 Dec;15(6):713-21. doi: 10.1007/s11307-013-0647-6.
We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors.
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.
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 (125)I-DKOP30 was significantly correlated with HIF-1-dependent luciferase bioluminescence, while that of (125)I-mDKOP was not.
(123)I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.
我们旨在开发一种用于成像缺氧诱导因子-1（HIF-1）活性肿瘤的放射性标记肽探针。
我们合成了含有或缺乏蛋白酶体中 HIF-1α 氧依赖性降解必需序列的肽探针（（123/125）I-DKOP30 或（125）I-mDKOP，分别）。使用含有蛋白酶体的细胞裂解物评估探针的体外降解情况。还进行了体内生物分布研究、平面成像、放射自显影以及探针积累与 HIF-1 转录活性之间的比较。
（125）I-DKOP30 以蛋白酶体依赖性方式降解，而（125）I-mDKOP 则未降解。生物分布分析显示（125）I-DKOP30 在肿瘤中的积累。通过体内成像可以清楚地观察到肿瘤，（125）I-DKOP30 的肿瘤内分布与 HIF-1α 阳性缺氧区域一致。（125）I-DKOP30 的肿瘤积累与 HIF-1 依赖性荧光素酶生物发光显著相关，而（125）I-mDKOP 则没有。
（123）I-DKOP30 是一种用于成像 HIF-1 活性肿瘤的有用肽探针。
