Molecular targeting of lymph nodes with L-selectin ligand-specific US contrast agent: A feasibility study in mice and dogs

Molecular targeting of lymph nodes with L-selectin ligand-specific US contrast agent: A feasibility study in mice and dogs
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DOI:
10.1148/radiol.2313030425
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发表时间:
2004-06-01
期刊:
影响因子:
19.7
通讯作者:
Schirner, M
Schirner, M
中科院分区:
医学1区
文献类型:
--
作者:
Hauff, P;Reinhardt, M;Schirner, M

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目的:探讨在正常条件下静脉注射L选择素配体特异性聚合物填充空气微粒(MPS)进行外周淋巴结主动靶向的可行性。材料和方法:3只清醒小鼠分别静脉注射L选择素配体特异性MPS和两种对照物质(免疫球蛋白M亚型MPS和天然MPS)(1.4×10(7)MPS/kg)。给药后30min处死所有小鼠。切除淋巴结(颈部、腹股沟、腋窝、延髓、肠系膜)、脾(阳性对照)和肾脏(血池对照),并在装有脱气水的水箱中用谐波彩色多普勒超声(US)检测MP相关的受激声发射(SAE)信号。在6只麻醉Beagel犬身上进行了第二次实验,使用相同的MP配方。每种MP制剂在两只麻醉犬中以单次静脉推注(1×10(7)MPS/kg)的形式给予。在给药30分钟后,用超声活体检测网窝淋巴结、脾(阳性对照)和肾脏(血池对照)中MP相关的SAE信号。结果:经L-选择素配体特异性MPS处理的所有小鼠(P=0.05)的淋巴结和两只犬的窝淋巴结均显示清晰的MP相关SAE信号,而接受对照物质的所有小鼠的淋巴结和4只犬的窝淋巴结均未显示任何与MP相关的SAE信号。结论:静脉注射L-选择素配体特异性US造影剂用于小鼠和犬主动淋巴结靶向治疗是可行的。(C)RSNA,2004年。
PURPOSE: To evaluate the feasibility of using intravenously administered L-selectin ligand-specific polymer-stabilized air-filled microparticles (MPs) for active targeting of peripheral lymph nodes under normal conditions in animal models.MATERIALS AND METHODS: L-selectin ligand-specific MPs and two control substances (immunoglobulin M-isotype MPs and native MPs) were each administered in three conscious mice as a single intravenous bolus injection (1.4 x 10(7) MPs/kg)(.) All mice were sacrificed 30 minutes after administration. Lymph nodes (cervical, inguinal, axillary, popliteal, mesenteric), spleen (positive control), and kidney (blood pool control) were removed and examined for MP-related stimulated acoustic emission (SAE) signals by using harmonic color Doppler ultrasonography (US) in a tank containing degassed water. A second experiment was performed in six anesthetized beagel dogs by using the same MP formulation. Each of the MP formulations was administered in two anesthetized dogs as a single intravenous bolus injection (1 x 10(7) MPs/kg). The popliteal lymph nodes, spleen (positive control), and kidney (blood pool control) were examined in vivo with US for MP-related SAE signals 30 minutes after administration. Fisher exact test for the one-side alternative was used for mouse data analysis.RESULTS: The lymph nodes of all mice (P = .05) and the popliteal lymph nodes of both dogs treated with L-selectin ligand-specific MPs showed clear MP-related SAE signals, whereas the lymph nodes of all mice and the popliteal lymph nodes of four dogs that received the control substances did not show any SAE signals.CONCLUSIONS: Use of an intravenously administered L-selectin ligand-specific US contrast agent is feasible for active lymph node targeting in mice and dogs. (C) RSNA, 2004.