MicroPET imaging of tumor angiogenesis and monitoring on antiangiogenic therapy with an 18F labeled RGD-based probe in SKOV-3 xenograft-bearing mice

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• 作者：Guangjie Yang ; Pei Nie ; Yu Kong ; Hukui Sun ; Guihua Hou ; Jiankui Han
• 关键词：Ovarian cancer ; Monitoring antiangiogenic therapy ; Target imaging ; RGD peptide ; Integrin imaging
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：36
• 期：5
• 页码：3285-3291
• 全文大小：3,236 KB
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• 作者单位：Guangjie Yang (1)
  Pei Nie (2)
  Yu Kong (1)
  Hukui Sun (3)
  Guihua Hou (3)
  Jiankui Han (1)
  
  1. Department of Nuclear Medicine, Qilu Hospital, Shandong University, No.107 Wenhuaxi Road, Jinan, Shandong, China
  2. Department of Radiology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
  3. Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan, Shandong, 250012, China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

So far, there is no satisfactory imaging modality to monitor antiangiogenesis therapy of ovarian cancer noninvasively. The aim of this study was to evaluate the effectiveness and sensibility of an 18F labeled Arg-Gly-Asp (RGD) peptide in imaging and monitoring antiangiogenic responds in SKOV-3 xenograft-bearing mice. 18F-FB-NH-PEG₄-E[PEG₄-c(RGDfK)]₂ (denoted as 18F-RGD₂) was synthesized and employed in this study. Mice bearing ovarian cancer SKOV-3 tumors were used for biodistribution and microPET imaging studies compared with 18F-FDG imaging. Animals were treated with low-dose paclitaxel and the effect of paclitaxel therapy on 18F-RGD₂ accumulation was investigated. Microvascular density (MVD) of SKOV-3 tumors was detected to assess the reliability of 18F-RGD₂ in antiangiogenesis monitoring. Biodistribution studies for 18F-RGD₂ revealed favorable in vivo pharmacokinetic properties, with significant levels of receptor-specific tumor uptake determined via blocking studies. MicroPET imaging results demonstrated high contrast visualization of SKOV-3 tumors. And tumor to background ratio (T/NT) of 18F-RGD₂ uptake was significantly higher than that of 18F-FDG. Studies on antiangiogenic therapy demonstrated percentage of injected dose per gram of tissue (%ID/g) tumor uptake of 18F-RGD₂ which was obviously decreased in the treatment group than the control group, especially at 60?min (by 31.31?±-.18?%, P--.009) and 120?min (by 38.92?±-.31?%, P-lt;-.001) after injection of 18F-RGD₂. MVD measurement of SKOV-3 tumors confirmed the finding of the biodistribution studies in monitoring antiangiogenesis therapy. 18F-RGD₂, with favorable biodistribution properties and specific affinity, is a promising tracer for tumor imaging and monitoring antiangiogenesis therapy in ovarian cancer SKOV-3 xenograft-bearing mice.