Thermoacoustic molecular tomography with magnetic nanoparticle contrast agents for targeted tumor detection

Thermoacoustic molecular tomography with magnetic nanoparticle contrast agents for targeted tumor detection
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使用磁性纳米颗粒造影剂进行热声分子断层扫描,用于靶向肿瘤检测

DOI:
10.1118/1.3466696
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发表时间:
2010-08-01
期刊:
影响因子:
3.8
通讯作者:
Xing, Da
Xing, Da
中科院分区:
医学3区
文献类型:
--
作者:
Nie, Liming;Ou, Zhongmin;Xing, Da

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目的:先前已经报道了在体模中证明微波诱导热声(TA)能力的主要可行性步骤。然而,迄今为止,在热声断层成像(达特)领域,还没有显示出针对活体受试者的病变部位。为了确定致癌表面分子的表达,有必要通过达特对肿瘤病灶进行成像并获得其致病状态。方法:与生物组织相比,氧化铁纳米颗粒具有更高的微波吸收率。在Fe 3 O 4超顺磁流体中,通过苯胺聚合制备了Fe 3 O 4/聚苯胺(PANI)纳米粒子。然后将Fe_3 O_4/PANI偶联到叶酸(FA)上,FA可以特异性结合到叶酸受体表面,作为肿瘤标志物。结果:在离体人血和小鼠尾中成功地观察到了Fe 3 O 4/PANI超顺磁性纳米粒子对达特图像的增强作用。将靶向纳米颗粒静脉注射给荷瘤小鼠,显示出比在肿瘤中注射非靶向纳米颗粒的小鼠大五倍的热声信号和长得多的消除时间。结论:首次报道了在分子水平上构建的与肿瘤配体偶联的氧化铁纳米粒子用于达特肿瘤的靶向检测。结果表明,功能化氧化铁纳米粒子的热声分子成像可能有助于靶向和功能性早期癌症成像。此外,与合适的肿瘤标记物组合的改性氧化铁纳米颗粒也可以用作用于靶向和引导癌症热治疗的新型纳米材料。(C)2010年美国医学物理学家协会。[DOI:10.1118/1.3466696]
Purpose: The primary feasibility steps of demonstrating the ability of microwave-induced thermoacoustic (TA) in phantoms have been previously reported. However, none were shown to target a diseased site in living subjects in thermoacoustic tomography (TAT) field so far. To determine the expressions of oncogenic surface molecules, it is quite necessary to image tumor lesions and acquire pathogenic status on them via TAT.Methods: Compared to biological tissues, iron oxide nanoparticles have a much higher microwave absorbance. Fe3O4/polyaniline (PANI) nanoparticles were prepared via polymerization of aniline in the Fe3O4 superparamagnetic fluids. Then Fe3O4/PANI was conjugated to folic acid (FA), which can bind specifically to the surface of the folate receptor used as a tumor marker. FA-Fe3O4/PANI targeted tumor was irradiated by pulsed microwave at 6 GHz for thermoacoustic detection and imaging.Results: The effect of the Fe3O4/PANI superparamagnetic nanoparticles for enhancing TAT images was successfully investigated in ex vivo human blood and in vivo mouse tail. Intravenous administration of the targeted nanoparticles to mice bearing tumors showed fivefold greater thermoacoustic signal and much longer elimination time than that of mice injected with nontargeted nanoparticles in the tumor. The specific targeting ability of FA-Fe3O4/PANI to tumor was also verified on fluorescence microscopy.Conclusions: Fabricated iron oxide nanoparticles conjugated with tumor ligands for targeted TAT tumor detection at the molecular level was reported for the first time. The results indicate that thermoacoustic molecular imaging with functionalized iron oxide nanoparticles may contribute to targeted and functional early cancer imaging. Also, the modified iron oxide nanoparticles combined with suitable tumor markers may also be used as novel nanomaterials for targeted and guided cancer thermal therapy. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3466696]