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

低氧诱导因子-1(HIF-1)在恶性肿瘤的发展过程中起着重要作用，在肿瘤对放射治疗的抵抗中起着重要作用。为了对HIF-1活性肿瘤进行成像，设计并合成了含有HIF-1a氧依赖降解必需序列的多肽探针(^I-DKOP30)。I-DKOP30在低氧细胞中的积聚明显高于常氧细胞。生物分布分析显示I-DKOP30在肿瘤中蓄积。活体成像显示肿瘤清晰，瘤内分布与HIF-1a阳性缺氧区一致。因此，^I-DKOP30是一种有用的多肽探针，可用于HIF-1活性肿瘤的显像。

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.