Molecular targeting of ultrasonographic contrast agent for detection of head and neck squamous cell carcinoma.

Molecular targeting of ultrasonographic contrast agent for detection of head and neck squamous cell carcinoma.
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DOI:
10.1001/archoto.2012.1081
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发表时间:
2012-07
影响因子:
--
通讯作者:
Rosenthal, Eben L.
Rosenthal, Eben L.
中科院分区:
其他
文献类型:
--
作者:
Knowles, Joseph A.;Heath, Cara H.;Saini, Reshu;Umphrey, Heidi;Warram, Jason;Hoyt, Kenneth;Rosenthal, Eben L.

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目的:探讨靶向造影剂在体外和体内超声显像头颈部肿瘤的可行性。我们假设微泡造影剂与肿瘤特异性抗体的结合可能提高头颈部鳞状细胞癌(HNSCC)的US检测。抗egfr和抗cd147微泡造影剂在HNSCC超声成像中的临床前盲法评估。动物研究。免疫缺陷小鼠。注射目标微泡。超声检测肿瘤微泡摄取。6种头颈癌细胞系中抗表皮生长因子受体(EGFR)和抗cd147靶向微泡的体外评估结果显示,它们比正常真皮成纤维细胞提高了6倍(P< 0.001)。在所有细胞系中,靶向药物与表皮生长因子受体(EGFR) (R2=0.81)和CD147 (R2=0.72)的表达均呈正相关。裸鼠(N=8)侧腹肿瘤的体内成像显示,抗egfr -和抗cd147靶向微泡剂比IgG对照组的分辨率更高(P< 0.001),而双靶向造影剂比单靶向造影剂的成像效果更高(P= 0.02和P= 0.05)。在一项盲法体内评估中,与对照组相比,靶向对比剂增加了侧腹肿瘤的肿瘤内增强。靶向美国造影剂对EGFR和CD147的检测对侧腹肿瘤的敏感性为100%,特异性为87%。本临床前研究证明了使用分子US靶向HNSCC进行HNSCC肿瘤体内对比增强成像的可行性。
To investigate the feasibility of ultrasonographic (US) imaging of head and neck cancer with targeted contrast agents both in vitro and in vivo. We hypothesize that conjugation of microbubble contrast agent to tumor-specific antibodies may improve US detection of head and neck squamous cell carcinoma (HNSCC). Preclinical blinded assessment of anti-EGFR and anti-CD147 microbubble contrast agents for US imaging of HNSCC. Animal study. Immunodeficient mice. Injection of targeted microbubbles. Microbubble uptake in tumors as detected by US. In vitro assessment of anti–epidermal growth factor receptor (EGFR) and anti-CD147–targeted micro-bubbles in 6 head and neck cancer cell lines yielded a 6-fold improvement over normal dermal fibroblasts (P<.001). Binding of targeted agents had a positive correlation to both epidermal growth factor receptor (EGFR) (R2=0.81) and CD147 (R2=0.72) expression among all cell lines. In vivo imaging of flank tumors in nude mice (N=8) yielded enhanced resolution of anti-EGFR– and anti-CD147–targeted microbubble agents over IgG control (P<.001), while dual-targeted contrast agents offered enhanced imaging over single-targeted contrast agents (P=.02 and P=.05, respectively). In a blinded in vivo assessment, targeted contrast agents increased intratumoral enhancement of flank tumors over controls. Targeted US contrast agents to both EGFR and CD147 were 100% sensitive and 87% specific in the detection of flank tumors. This preclinical study demonstrates feasibility of using molecular US to target HNSCC for contrast-enhanced imaging of HNSCC tumor in vivo.
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发表时间: 2008-11
影响因子: --
作者:
Newman, J. Robert;Bohannon, Isaac A.;Zhang, Wenyue;Skipper, Joni B.;Grizzle, William E.;Rosenthal, Eben L.
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