LodeSpin Labs, Seattle, WA 98195, USA.
Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
Nanoscale. 2017 Jan 19;9(3):1299-1306. doi: 10.1039/c6nr08468k.
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 X-ray 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 a 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 (t) would be a versatile MPI tracer with widespread applications. Here we show that a long circulating polyethylene glycol (PEG)-coated SPIO tracer, LS-008, provides excellent colloidal stability and a persistent intravascular MPI signal, showing its potential as the first blood pool tracer optimized for MPI. We evaluated variations of PEG coating and found that colloidal stability of tracers improved with the increasing PEG molecular weight (keeping PEG loading constant). Blood circulation in mice, evaluated using Magnetic Particle Spectrometry (MPS), showed that the t 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 t of about 105 minutes in mice. In vivo MPI imaging with LS-008 using a 7 T/m/μ 3D x-space MPI mouse scanner revealed a prolonged intravascular signal (3-5 hours) post-injection. Our results show the optimized magnetic properties and long systemic retention of LS-008 making 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.
超顺磁性氧化铁（SPIO）纳米颗粒具有优化和良好表征的特性对于磁共振粒子成像（MPI）至关重要。MPI 是一种新型的体内成像方式，有望整合 X 射线 CT 的速度、MRI 的安全性和 PET 的灵敏度。由于 SPIOs 是 MPI 信号的来源，因此必须优化核心和表面特性，以实现针对特定成像应用量身定制的药代动力学的高效体内成像。现有的 SPIOs 如 Resovist（ferucarbotran）提供了不理想的 MPI 信号，并且由于快速的全身清除而进一步限制了 MPI 的体内实用性。具有长血液半衰期（t）的 SPIO 试剂将是一种多功能的 MPI 示踪剂，具有广泛的应用。在这里，我们展示了一种长循环聚乙二醇（PEG）涂层 SPIO 示踪剂 LS-008，它提供了极好的胶体稳定性和持久的血管内 MPI 信号，显示了其作为第一个针对 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 PEG 分子量的增加而提高（保持 PEG 负载不变）。使用磁粒子光谱法（MPS）评估小鼠的血液循环，结果表明 SPIO 示踪剂的 t 随 PEG 分子量和负载而变化。用 20 kDa PEG 以 18.8%的载量涂层的 LS-008，在小鼠体内提供了最有前途的长期胶体稳定性，t 约为 105 分钟。使用 7 T/m/μ3D x-space MPI 小鼠扫描仪进行 LS-008 的体内 MPI 成像显示，注射后血管内信号延长（3-5 小时）。我们的结果表明 LS-008 具有优化的磁性能和长的系统保留时间，使其成为一种有前途的血池 MPI 示踪剂，有望在心血管和脑血管疾病模型以及通过增强渗透和保留进行的实体瘤定量和成像中实现 MPI 成像。
