Evaluation of PEG-coated iron oxide nanoparticles as blood pool tracers for preclinical magnetic particle imaging.
Evaluation of PEG-coated iron oxide nanoparticles as blood pool tracers for preclinical magnetic particle imaging.
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DOI：
10.1039/c6nr08468k
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发表时间：
2017-01-19
期刊：
影响因子：
6.7
通讯作者：
Krishnan KM
中科院分区：
文献类型：
--
作者：
Khandhar AP;Keselman P;Kemp SJ;Ferguson RM;Goodwill PW;Conolly SM;Krishnan KM
具有优化和良好表征特性的超顺磁性氧化铁（SPIO）纳米颗粒对于磁粒子成像（MPI）至关重要。MPI是一种新型体内成像模式，有望整合CT的速度、MRI的安全性和PET的灵敏度。由于SPIO是MPI信号的来源，因此必须优化核心和表面性质，以实现针对特定成像应用定制的药代动力学的有效体内成像。现有的SPIO如Resovist（ferucarbotran）提供次优的MPI信号，并且由于快速的全身清除而进一步限制MPI的体内效用。具有长血液半衰期（t1/2）的SPIO试剂将是具有广泛应用的通用MPI示踪剂。在这里，我们展示了长循环聚乙二醇（PEG）涂层SPIO示踪剂LS-008，提供了优异的胶体稳定性和持久的血管内MPI信号，显示出作为第一个针对MPI优化的血池示踪剂的潜力。我们评估了PEG涂层的变化，发现示踪剂的胶体稳定性随着PEG分子量的增加而提高（保持PEG负载恒定）。使用磁粒子光谱法（MPS）评价的小鼠血液循环表明，SPIO示踪剂的t1/2随PEG分子量和载量而变化。LS-008包被有20 kDa PEG，载量为18.8%，在小鼠中提供了最有希望的长期胶体稳定性，t1/2约为105分钟。在7 T/m/μ0 3D x空间MPI小鼠扫描仪中使用LS-008的体内MPI成像显示注射后延长的血管内信号（3-5小时）。我们的结果显示LS-008的优化的磁性和长的全身保留使其成为有前景的血池MPI示踪剂，具有在心血管和脑血管疾病模型中实现MPI成像以及通过增强的渗透和保留实现实体肿瘤定量和成像的潜力。
Superparamagnetic iron oxide (SPIO) nanoparticles with optimized and well-characterized properties are critical for Magnetic Particle Imaging (MPI). MPI is a novel in vivo imaging modality that promises to integrate the speed of CT, safety of MRI and sensitivity of PET. Since SPIOs are the source of MPI signal, both the core and surface properties must be optimized to enable efficient in vivo imaging with pharmacokinetics tailored for specific imaging applications. Existing SPIOs like Resovist (ferucarbotran) provide suboptimal MPI signal, and further limit MPI's in vivo utility due to rapid systemic clearance. An SPIO agent with a long blood half-life (t1/2) would be a versatile MPI tracer with widespread applications. Here we show a long circulating polyethylene glycol (PEG)-coated SPIO tracer, LS-008, provides excellent colloidal stability and persistent intravascular MPI signal, showing potential as the first blood pool tracer optimized for MPI. We evaluated variations of the PEG coating and found that colloidal stability of tracers improved with increasing PEG molecular weight (keeping PEG loading constant). Blood circulation in mice, evaluated using Magnetic Particle Spectrometry (MPS), showed that t1/2 of SPIO tracers varied with both PEG molecular weight and loading. LS-008, coated with 20 kDa PEG at 18.8% loading capacity, provided the most promising long-term colloidal stability with a t1/2 of about 105 minutes in mice. In vivo MPI imaging with LS-008 in a 7 T/m/μ0 3D x-space MPI mouse scanner revealed a prolonged intravascular signal (3-5 hours) post-injection. Our results show the optimized magnetic properties a nd long systemic retention of LS-008 make it a promising blood pool MPI tracer, with potential to enable MPI imaging in cardio - and cerebrovascular disease models, and solid tumor quantification and imaging via enhanced permeation and retention.