MR and CT Contrast Media Research, Bayer Pharma AG, Berlin, Germany.
Int J Nanomedicine. 2012;7:4447-58. doi: 10.2147/IJN.S33120. Epub 2012 Aug 10.
Magnetic resonance imaging (MRI), one of the most powerful imaging techniques available, usually requires the use of an on-demand designed contrast agent to fully exploit its potential. The blood kinetics of the contrast agent represent an important factor that needs to be considered depending on the objective of the medical examination. For particulate contrast agents, such as superparamagnetic iron oxide nanoparticles (SPIOs), the key parameters are particle size and characteristics of the coating material. In this study we analyzed the effect of these two properties independently and systematically on the magnetic behavior and blood half-life of SPIOs.
Eleven different SPIOs were synthesized for this study. In the first set (a), seven carboxydextran (CDX)-coated SPIOs of different sizes (19-86 nm) were obtained by fractionating a broadly size-distributed CDX-SPIO. The second set (b) contained three SPIOs of identical size (50 nm) that were stabilized with different coating materials, polyacrylic acid (PAA), poly-ethylene glycol, and starch. Furthermore, small PAA-SPIOs (20 nm) were synthesized to gain a global insight into the effects of particle size vs coating characteristics. Saturation magnetization and proton relaxivity were determined to represent the magnetic and imaging properties. The blood half-life was analyzed in rats using MRI, time-domain nuclear magnetic resonance, and inductively coupled plasma optical emission spectrometry.
By changing the particle size without modifying any other parameters, the relaxivity r(2) increased with increasing mean particle diameter. However, the blood half-life was shorter for larger particles. The effect of the coating material on magnetic properties was less pronounced, but it had a strong influence on blood kinetics depending on the ionic character of the coating material.
In this report we systematically demonstrated that both particle size and coating material influence blood kinetics and magnetic properties of SPIO independently. These data provide key information for the selection of a contrast agent for a defined application and are additionally valuable for other nano areas, such as hyperthermia, drug delivery, and nanotoxicology.
磁共振成像（MRI）是目前最强大的成像技术之一，通常需要使用按需设计的对比剂来充分发挥其潜力。对比剂的血液动力学是需要考虑的一个重要因素，具体取决于医学检查的目的。对于颗粒状对比剂，如超顺磁氧化铁纳米颗粒（SPIOs），关键参数是颗粒大小和涂层材料的特性。在这项研究中，我们独立地和系统地分析了这两个特性对 SPIOs 的磁性行为和血液半衰期的影响。
本研究共合成了 11 种不同的 SPIOs。在第一组（a）中，通过对广泛分布的羧基葡聚糖（CDX）-SPIOs 进行分级，获得了七种不同大小（19-86nm）的 CDX-SPIOs。第二组（b）包含三种大小相同（50nm）的 SPIOs，它们分别用不同的涂层材料稳定，即聚丙烯酸（PAA）、聚乙二醇和淀粉。此外，还合成了小的 PAA-SPIOs（20nm），以全面了解粒径与涂层特性的影响。通过测定饱和磁化强度和质子弛豫率来代表磁性和成像特性。通过 MRI、时域核磁共振和电感耦合等离子体光发射光谱法在大鼠体内分析血液半衰期。
通过改变颗粒大小而不改变任何其他参数，可以发现弛豫率 r(2)随着平均粒径的增加而增加。然而，较大的颗粒具有较短的血液半衰期。涂层材料对磁性性质的影响较小，但取决于涂层材料的离子特性，对血液动力学有很强的影响。
在本报告中，我们系统地证明了颗粒大小和涂层材料独立地影响 SPIOs 的血液动力学和磁性性质。这些数据为选择特定应用的对比剂提供了关键信息，并且对其他纳米领域（如热疗、药物传递和纳米毒理学）也具有重要价值。
