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（HIF-1）在恶性肿瘤的进展和放疗抵抗的发展中起重要作用。为了对HIF-1活性肿瘤成像，设计并合成了一种肽探针（Δ I-DKOP 30），其含有HIF-1 α氧依赖性降解的必需序列。在缺氧细胞中，DKOP 30的蓄积量高于常氧细胞。生物分布分析显示，在肿瘤中积累了14 I-DKOP 30。通过体内成像可以清楚地观察到肿瘤，并且肿瘤内^I-DKOP 30的分布与HIF-1a阳性缺氧区域一致。因此，1-DKOP 30是用于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.