Synthesis, characterization, and biodistribution of multiple 89Zr-labeled pore-expanded mesoporous silica nanoparticles for PET
Synthesis, characterization, and biodistribution of multiple 89Zr-labeled pore-expanded mesoporous silica nanoparticles for PET
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DOI：
10.1039/c3nr06800e
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发表时间：
2014-01-01
期刊：
影响因子：
6.7
通讯作者：
Linden, Mika
中科院分区：
文献类型：
--
作者：
Miller, Larissa;Winter, Gordon;Linden, Mika
功能性纳米颗粒是正电子发射断层扫描（PET）非常有趣的显像剂，因为正电子发射放射性核素可能多次掺入，从而增加了信号强度。此外，携带长寿命同位素的纳米颗粒可以实现具有更高信噪比的长期纳米颗粒生物分布测试。介孔二氧化硅纳米颗粒（MSNs）近年来作为显像剂和体内体外药物载体引起了人们的广泛关注。在这里，我们展示了与携带长寿命Zr-89同位素（半衰期为78.4小时）的PET可成像MSNs的合成有关的结果。在这里，Zr-89（4+）通过络合剂对异硫氰酸atobyldeferrioxamine （DFO-NCS）共价附着在大孔msn上。由于msn上存在高DFO含量，在几分钟内即可实现Zr-89（4+）的定量标记，并且无需后续纯化步骤即可去除非络合的Zr-89（4+）。Zr-89标记的MSNs对Zr-89（4+）浸出的稳定性进行了24小时的验证。Zr-89-DFO-MSNs的高信号强度通过小鼠模型的PET成像得到了证明，其颗粒负荷比之前PET- msn研究中应用的颗粒负荷低一个数量级。不同尺寸和表面功能的微微颗粒的生物分布趋势与之前观察到的相同。综上所述，我们的研究结果表明，zr -89- dfo - msn是一种很有前景的PET显像剂，用于长期体内成像。
Functional nanoparticles are highly interesting imaging agents for positron emission tomography (PET) due to the possibility of multiple incorporation of positron emitting radionuclides thus increasing the signal strength. Furthermore, long-term nanoparticle biodistribution tests with increased signal-to-noise ratio can be achieved with nanoparticles carrying long-lived isotopes. Mesoporous silica nanoparticles, MSNs, have recently attracted a lot of interest as both imaging agents and carriers for drugs in vitro and in vivo. Here we present results related to the synthesis of PET imageable MSNs carrying the long-lived Zr-89 isotope (half-life of 78.4 hours). Here, Zr-89(4+) was immobilized through covalent attachment of the complexing agent p-isothiocyanatobenzyldesferrioxamine (DFO-NCS) to large-pore MSNs. Due to the presence of the high DFO content on the MSNs, quantitative Zr-89(4+) labeling was achieved within just a few minutes, and no subsequent purification step was needed in order to remove non-complexed Zr-89(4+). The stability of the Zr-89-labeled MSNs against leaching of Zr-89(4+) was verified for 24 hours. The high signal strength of the Zr-89-DFO-MSNs was evidenced by successful PET imaging using a mouse model at particle loadings one order of magnitude lower than those previously applied in PET-MSN studies. The biodistribution followed the same trends as previously observed for MSNs of different sizes and surface functionalities. Taken together, our results suggest that Zr-89-DFO-MSNs are promising PET imaging agents for long-term in vivo imaging.