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噬菌体展示源性多肽在骨肉瘤成像中的应用 |
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Phage display-derived peptides for osteosarcoma imaging |
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Sun X, Niu G, Yan Y, Yang M, Chen K, Ma Y, Chan N, Shen B, Chen X 2010/9/13 9:10:00 |
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Clinical Cancer Research, 2010, Volume 16, Issue 16
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Purpose: Osteosarcoma represents the most common malignant primary bone tumor in childhood, however, the survival rate has remained unchanged for the past 20 years. To improve existing diagnosis and treatment methods and broaden the spectrum of imaging agents that can be used for early detection and assessment of tumor response to therapy, we performed a phage display-based screening for peptide sequences that bind specifically to osteosarcoma cells. Experimental Design: From the Ph.D.-12 phage display peptide library composed of 2.7 × 109 different displayed peptides, one peptide was enriched after four rounds of in vitro selection in 143B osteosarcoma tumor cells with 293T human embryonic kidney cells as a control. Both the peptide and the phage clone displaying the peptide were conjugated with fluorescent dyes for in vitro cell and ex vivo tumor tissue stainings. The peptide was further labeled with 18F for positron emission tomography imaging studies. Cell uptake and efflux and ex vivo biodistribution were also done with 18F-labeled osteosarcoma specific peptide. Results: ASGALSPSRLDT was the dominant sequence isolated from biopanning and named as OSP-1. OSP-1 shares a significant homology with heparinase II/III family protein, which binds and reacts with heparan sulfate proteoglycans. The fluorescence staining showed that FITC-OSP-1-phage or Cy5.5-OSP-1 had high binding with a panel of osteosarcoma cell lines, much less binding with UM-SCC1 human head and neck squamous cell carcinoma cells, and almost no binding with 293T cells, whereas the scrambled peptide OSP-S had virtually no binding to all the cell lines. 18F-OSP-1 had significantly higher accumulation in 143B tumor cells both in vitro and in vivo than 18F-OSP-S. 18F-OSP-1 also had higher uptake in 143B tumors than in UM-SCC-1 tumors. Conclusions: Our data suggest that OSP-1 peptide is osteosarcoma specific, and the binding site of OSP-1 might be related to heparan sulfate proteoglycans. Appropriately labeled OSP-1 peptide has the potential to serve as a novel probe for osteosarcoma imaging. ©2010 AACR.
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Correspondence Address: Shen, B; Department of Medical Imaging and Nuclear Medicine, Fourth Hospital of Harbin Medical University, 31 Yinhang Street, Nangang District, Harbin 150001, China, email:shenbzh@vip.sina.com |
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疾病资源中心
王燕燕 王曙
上海交通大学附属瑞金医院内分泌科
患者,女,69岁。2009年1月无明显诱因下出现乏力,当时程度较轻,未予以重视。2009年3月患者乏力症状加重,尿色逐渐加深,大便习惯改变,颜色变淡。4月18日入我院感染科治疗,诉轻度头晕、心慌,体重减轻10kg。无肝区疼痛,无发热,无腹痛、腹泻、腹胀、里急后重,无恶性、呕吐等。入院半月前于外院就诊,查肝功能:ALT 601IU/L,AST 785IU/L,TBIL 97.7umol/L,白蛋白 41g/L,甲状腺功能:游离T3 30.6pmol/L,游离T4 51.9pmol/L,心电图示快速房颤。
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