PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel 18F-Labeled Biotin Derivative
PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel 18F-Labeled Biotin Derivative
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DOI：
10.1007/s11307-010-0418-6
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发表时间：
2011-10-01
影响因子：
3.1
通讯作者：
Saji, Hideo
中科院分区：
文献类型：
--
作者：
Kudo, Takashi;Ueda, Masashi;Saji, Hideo
我们的目的是评估使用基于链霉亲和素-生物素的预靶向用于缺氧诱导因子（HIF）-1活性肿瘤的正电子发射断层扫描（PET）成像的可行性。（4-F-18-氟苯甲酰基）降生物素酰胺（F-18-FBB），一种放射性标记的生物素衍生物，用于进行生物分布研究和PET成像。将肿瘤F-18-FBB积累与HIF-1依赖性荧光素酶生物发光和HIF-1 α免疫组织化学信号进行比较。在小鼠的POS预靶向肿瘤中观察到F-18-FBB积累（3小时时每克2.85 +/-0.55%注射剂量），并在相同时间点获得清晰的PET图像。肿瘤内F-18-FBB的聚集与荧光素酶的生物发光强度呈正相关（R = 0.72，P < 0.05），且大多数聚集区域对应于HIF-1 α阳性区域，POS和F-18-FBB预靶向是肿瘤内HIF-1活性区域PET显像的有效方法。
We aimed to evaluate the feasibility of using streptavidin-biotin-based pretargeting for positron emission tomography (PET) imaging of hypoxia-inducible factor (HIF)-1-active tumors.We used POS, a genetically engineered form of streptavidin that selectively stabilizes in HIF-1-active cells, and (4-F-18-fluorobenzoyl)norbiotinamide (F-18-FBB), a radiolabeled biotin derivative, for performing a biodistribution study and for PET imaging. The tumoral F-18-FBB accumulation was compared to the HIF-1-dependent luciferase bioluminescence and HIF-1 alpha immunohistochemical signal.F-18-FBB accumulation was observed in POS-pretargeted tumors in mice (2.85 +/- 0.55% injected dose per gram at 3 h), and clear PET images were obtained at the same time point. The tumoral F-18-FBB accumulation positively correlated with luciferase bioluminescence (R = 0.72, P < 0.05), and most of the area showing F-18-FBB accumulation corresponded to HIF-1 alpha-positive areas.Pretargeting with POS and F-18-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.