In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents.
In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents.
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DOI：
10.1016/j.biomaterials.2015.02.040
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发表时间：
2015-06
期刊：
影响因子：
14
通讯作者：
Krishnan, Kannan M.
中科院分区：
文献类型：
--
作者：
Arami, Hamed;Khandhar, Amit P.;Tomitaka, Asahi;Yu, Elaine;Goodwill, Patrick W.;Conolly, Steven M.;Krishnan, Kannan M.
关键词：
磁粒子成像(MPI)是一种使用安全的磁性纳米粒子作为示踪剂的新型非侵入性生物医学成像方式。控制合成具有可调谐尺寸相关磁弛豫特性的纳米氧化铁(NPs)是发展MPI的关键。将这些纳米粒子用于其他成像手段(如核磁共振成像和荧光成像)的额外功能化将加快基于它们在临床前试验中的体外和体内表现的MPI示踪剂的筛选。在这里，我们通过酰胺键将两种不同类型的聚乙二醇(NH_2-PEG-NH_2和NH_2-PEGFMOC)偶联到单分散的19.7 nm纳米颗粒。此外，我们用Cy5.5标记了这些NPs的近红外荧光(NIRF)分子。双官能团聚乙二醇(NH2-PEG-NH2)由于颗粒间的交联作用，使示踪剂具有较大的流体力学尺寸(~98 nm比~43 nm)。这种簇的形成影响了这些示踪剂的多模式成像性能和药代动力学。我们发现，示踪剂在血液中的MPI信号强度取决于它们的血浆清除药代动力学。用MPI/MRI/NIRF研究注射后NPs的生物分布，发现其主要分布在肝脏和脾脏。来自切除器官的MPI和NIRF信号进一步证实了示踪剂的生物分布及其清除途径，其中Cy5.5标记使示踪剂在组织切片中的详细解剖图谱得以实现。这些多模式MPI示踪剂结合了每种成像模式的优点(例如分辨率、示踪剂灵敏度和临床使用可行性)，为各种体外和体内MPI应用铺平了道路。
Magnetic Particle Imaging (MPI) is a novel non-invasive biomedical imaging modality that uses safe magnetite nanoparticles as tracers. Controlled synthesis of iron oxide nanoparticles (NPs) with tuned size-dependent magnetic relaxation properties is critical for the development of MPI. Additional functionalization of these NPs for other imaging modalities (e.g. MRI and fluorescent imaging) would accelerate screening of the MPI tracers based on their in vitro and in vivo performance in pre-clinical trials. Here, we conjugated two different types of poly-ethylene-glycols (NH2-PEG-NH2 and NH2-PEG FMOC) to monodisperse carboxylated 19.7nm NPs by amide bonding. Further, we labeled these NPs with Cy5.5 near infra-red fluorescent (NIRF) molecules. Bi-functional PEG (NH2-PEG-NH2) resulted in larger hydrodynamic size (~98nm vs. ~43nm) of the tracers, due to interparticle crosslinking. Formation of such clusters impacted the multimodal imaging performance and pharmacokinetics of these tracers. We found that MPI signal intensity of the tracers in blood depends on their plasmatic clearance pharmacokinetics. Whole body mice MPI/MRI/NIRF, used to study the biodistribution of the injected NPs, showed primary distribution in liver and spleen. Biodistribution of tracers and their clearance pathway was further confirmed by MPI and NIRF signals from the excised organs where the Cy5.5 labeling enabled detailed anatomical mapping of the tracers.in tissue sections. These multimodal MPI tracers, combining the strengths of each imaging modality (e.g. resolution, tracer sensitivity and clinical use feasibility) pave the way for various in vitro and in vivo MPI applications.
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