Departments of Electrical Engineering and Computer Science and Materials Science and Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2014 May 6;111(18):6588-93. doi: 10.1073/pnas.1400015111. Epub 2014 Apr 21.
Targeted MRI contrast agents have proven useful in research and clinical studies for highlighting specific metabolites and biomarkers [Davies GL, et al. (2013) Chem Commun (Camb) 49(84):9704-9721] but their applicability in serial imaging is limited owing to a changing concentration postinjection. Solid enclosures have previously been used to keep the local concentration of contrast agent constant, but the need to surgically implant these devices limits their use [Daniel K, et al. (2009) Biosens Bioelectron 24(11):3252-3257]. This paper describes a novel class of contrast agent that comprises a responsive material for contrast generation and an injectable polymeric matrix for structural support. Using this principle, we have designed a contrast agent sensitive to oxygen, which is composed of dodecamethylpentasiloxane as the responsive material and polydimethylsiloxane as the matrix material. A rodent inspired-gas model demonstrated that these materials are functionally stable in vivo for at least 1 mo, which represents an order of magnitude improvement over an injection of liquid siloxane [Kodibagkar VD, et al. (2006) Magn Reson Med 55(4):743-748]. We also observed minimal adverse tissue reactions or migration of contrast agents from the initial injection site. This class of contrast agents, thus, represented a new and complementary method to monitor chronic diseases by MRI.
靶向 MRI 对比剂在研究和临床研究中已被证明对突出特定代谢物和生物标志物很有用 [Davies GL 等人(2013 年)Chem Commun(Camb)49(84):9704-9721],但由于注射后浓度不断变化,其在连续成像中的应用受到限制。以前曾使用固体外壳来保持对比剂的局部浓度恒定,但由于需要手术植入这些设备,限制了它们的使用 [Daniel K 等人(2009 年)Biosens Bioelectron 24(11):3252-3257]。本文介绍了一类新的对比剂,它由用于对比生成的响应材料和用于结构支撑的可注射聚合物基质组成。使用这一原理,我们设计了一种对氧气敏感的对比剂,它由十二甲基环五硅氧烷作为响应材料和聚二甲基硅氧烷作为基质材料组成。一种受啮齿动物启发的气体模型表明,这些材料在体内至少稳定 1 个月,这比注射液体硅氧烷有了一个数量级的改进 [Kodibagkar VD 等人(2006 年)Magn Reson Med 55(4):743-748]。我们还观察到对比剂从初始注射部位的最小组织不良反应或迁移。因此,这类对比剂代表了一种新的、互补的 MRI 监测慢性疾病的方法。