Improved Molecular Contrast Agent for MRI Imaging

描述(申请人提供)：提出了一种分子靶向磁共振T2造影剂，该造影剂被合成以最大限度地提高周围组织和生物流体质子的自旋-自旋松弛。通过在我们小组以前工作的基础上，单个Fe304纳米晶体将被几何优化和脂钝化，以最大化T2驰豫效应，特别是通过最大化磁各向异性参数和旋转关联时间。因此，当分子靶向低浓度的致病分子时，由于信号强度较差，这些靶向特定的纳米颗粒将提供可能的最大信号强度增量。通过这种方式，我们打算改进现有的Fe3O4纳米粒子T2弛豫剂，在分子成像研究文献中报道。最后，我们建议使用我们设计的造影剂来靶向心脏移植排斥反应，从而补充机构的目标，即连接物理科学和生命科学，以促进医疗保健。具体目标：1)合成/功能化；2)表征；3)检测我们的形状/表面改变的、磁性优化的靶向T2造影剂与心脏移植排斥反应期间表达的受体(通过MRI)。研究设计和方法：有机金属前驱体在高温下分解，得到高度各向异性的定制磁性纳米颗粒。这些磁性纳米粒子将通过脂质/抗体单分子层进行功能化，并通过透射电子显微镜、X射线衍射、流式细胞仪、超导量子干涉装置磁测量、核磁共振色散和1.5/4.7T磁共振成像进行表征。公共卫生相关性：心脏移植的急性排斥反应是术后死亡率的主要原因，可导致移植后第一年的死亡率为20%，随后几年的死亡率高达15%。目前评估排斥反应的标准包括通过活检检查免疫激活，这是一种高度侵入性的技术，需要医生在移植后进行大量随访，并要求患者承诺在其余生中忍受常规的活检程序。因此，需要一种非侵入性的方法来检测心脏移植患者的排斥反应。

DESCRIPTION (provided by applicant): A molecularly targeted MRI T2 contrast agent, synthesized to maximize the spin-spin relaxation of surrounding tissue and biofluid protons is proposed. By building on previous work in our group, individual Fe304 nanocrystals will be geometrically optimized and lipid-passivated to maximize the T2 relaxation effect, specifically by maximizing the magnetic anisotropy parameters and rotational correlation time. Thus, given poor signal intensities when molecularly targeting low concentrations of pathogenic molecules, these target specific nanoparticles will provide the greatest possible signal intensity delta. In this fashion, we intend to improve on existing Fe3O4 nanoparticle T2 relaxation agents reported in the molecular imaging research literature. Finally, we propose to use our designed contrast agent to target cardiac transplant rejection, thereby complementing the agency goal of bridging physical sciences and life sciences to advance medical care. Specific Aims: 1) Synthesize/Functionalize; 2) Characterize; and 3) Detect our shape/surface altered, magnetically optimized, targeted T2 contrast agent to receptors expressed during cardiac transplant rejection (via MRI). Research Design and Methods: Organo-metallic precursors are decomposed at high temperatures to yield highly anisotropic custom magnetic nanoparticles. These magnetic nanoparticles will be functionalized with a lipid/antibody monolayer and characterized via transmission electron microscopy, X-ray diffraction, flow cytometry, superconducting quantum interference device magnetometry, nuclear magnetic resonance dispersion, and 1.5/4.7 T magnetic resonance imaging. Public Health Relevance: Acute rejection in cardiac transplant is a leading reason for post-surgery mortality and can result in mortality rates of 20% in the first year post-transplant and up to 15 % in subsequent years. Current standards for evaluating rejection involve examination of immune activation via biopsy, which is a highly invasive technique that demands significant post-transplant follow-up by the physician and commitment by the patients to endure routine biopsy procedures for the rest of their lives. Thus, the need for a non-invasive method to detect rejection episodes in cardiac transplant patients is especially acute.