Development of a radioactive low-molecular weight probe for the specific imaging of HIF-1-active hypoxic tumors

缺氧诱导因子-1 （Hypoxia-inducible factor-1, HIF-1）在恶性肿瘤的进展和放疗耐药过程中起重要作用。为了成像hif -1活性肿瘤，设计并合成了一种肽探针（^I-DKOP30），该探针含有HIF-1a氧依赖性降解的基本序列。^I-DKOP30在缺氧细胞中的积累量高于常氧细胞。生物分布分析显示^I-DKOP30在肿瘤中积累。体内显像显示肿瘤清晰，肿瘤内^I-DKOP30的分布与hif -1a阳性缺氧区吻合。因此，^I-DKOP30是hif -1活性肿瘤成像的有用肽探针。

Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumor progression and in the development of resistance to radiotherapy. To image HIF-1-active tumors, a peptide probe (^I-DKOP30) was designed and synthesized that contains an essential sequence of the oxygen-dependent degradation of HIF-1a. ^I-DKOP30 showed higher accumulation in hypoxic cells than normoxic cells. Biodistribution analysis showed ^I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivoimaging, and intratumoral distribution of ^I-DKOP30 coincided with the HIF-1a-positive hypoxic regions. Thus, ^I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.