(⁹⁹m)Tc-bisphosphonate-iron oxide nanoparticle conjugates for dual-modality biomedical imaging.

(⁹⁹m)Tc-bisphosphonate-iron oxide nanoparticle conjugates for dual-modality biomedical imaging.
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DOI:
10.1021/bc100483k
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发表时间:
2011-03-16
影响因子:
4.7
通讯作者:
Blower PJ
Blower PJ
中科院分区:
化学2区
文献类型:
--
作者:
Torres Martin de Rosales R;Tavaré R;Glaria A;Varma G;Protti A;Blower PJ

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基于放射性核素的单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET)与磁共振成像(MRI)的结合有望成为下一代临床扫描仪。因此,人们对SPECT-和PET-MRI试剂的开发越来越感兴趣。为此,我们报道了一类基于放射性标记双膦酸盐(BP)直接偶联到超顺磁性氧化铁(SPIO)纳米颗粒表面的新型双模式显像剂。我们展示了BP-氧化铁结合的高潜力,使用99mTC-二吡啶甲胺(DPA)-阿伦磷酸(BP-SPECT)试剂和Endorem/Feridex(基于SPIO的肝脏MRI造影剂)。在室温下,如果SPIO没有被有机聚合物包覆,99mTC-DPA-阿伦磷酸酯可以一步标记SPIO。如果纳米颗粒被包覆,则需要加热,只要包覆层像Endorem中的葡聚糖那样结合较弱即可。用透射电子显微镜(5 nm,Fe3O4核)和差示扫描量热法(106±60 nm,Fe3O4核+葡聚糖)对99mTC-DPA-ALE-Endorem进行了表征。EDX、Dittmer-Lester和放射性标记研究表明,BP与纳米颗粒结合,它与Endorem的Fe3O4核心结合,而不是与其葡聚糖涂层结合。核磁共振和纳米SPECT-CT成像证实了这些纳米粒子的双峰成像能力和良好的稳定性,表明99mTC和Endorem在体内共定位于肝和脾,与99mTC-DPA-ALE-Endorem的组成和大小不谋而合。据我们所知,这是第一个用BP偶联物标记SPIO的例子,也是第一个直接在氧化铁核心表面而不是其涂层上标记SPIO纳米粒子的例子。这项工作为新一代SPECT/PET-MR显像剂奠定了基础,在这种显像剂中,BP基团可以使用非常简单的方法将功能附加到Fe3O4纳米粒子上,从而提供靶向、隐形/稳定和放射性核素。
The combination of radionuclide-based imaging modalities such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) with magnetic resonance imaging (MRI) is likely to become the next generation of clinical scanners. Hence, there is a growing interest in the development of SPECT- and PET-MRI agents. To this end, we report a new class of dual-modality imaging agents based on the conjugation of radiolabeled bisphosphonate (BP) directly to the surface of superparamagnetic iron oxide (SPIO) nanoparticles. We demonstrate the high potential of the BP-iron oxide conjugation using 99mTc-dipicolylamine(DPA)-alendronate, a BP-SPECT agent, and Endorem/Feridex, a liver MRI contrast agent based on SPIO. The labeling of SPIOs with 99mTc-DPA-alendronate can be performed in one step at room temperature if the SPIO is not coated with an organic polymer. Heating is needed if the nanoparticles are coated, as long as the coating is weakly bound as in the case of dextran in Endorem. The size of the radiolabeled Endorem (99mTc-DPA-ale-Endorem) was characterized by TEM (5 nm, Fe3O4 core) and DLS (106 ± 60 nm, Fe3O4 core + dextran). EDX, Dittmer-Lester and radiolabeling studies demonstrate that the BP is bound to the nanoparticles and that it binds to the Fe3O4 cores of Endorem, and not its dextran coating. The bimodal imaging capabilities and excellent stability of these nanoparticles were confirmed using MRI and nanoSPECT-CT imaging, showing that 99mTc and Endorem co-localize in the liver and spleen in vivo, as expected for particles of the composition and size of 99mTc-DPA-ale-Endorem. To the best of our knowledge, this is the first example of radiolabeling SPIOs with BP conjugates and the first example of radiolabeling SPIO nanoparticles directly onto the surface of the iron oxide core, and not its coating. This work lays down the basis for a new generation of SPECT/PET-MR imaging agents in which the BP group could be used to attach functionality to provide targeting, stealth/stability and radionuclides to Fe3O4 nanoparticles using very simple methodology readily amenable to GMP.
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发表时间: 2009-08-28
期刊: Chemical communications (Cambridge, England)
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发表时间: 2007-03-07
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