Designing Magnetic Resonance Protein-based Contrast Agents with High Relaxivity

磁共振成像（MRI）是一种强大的非侵入性工具，具有高空间分辨率，可用于临床 诊断不受组织深度的限制。MRI技术应用的主要障碍是 缺乏敏感性和特异性。该方法常规地使用造影剂来放大造影剂中的对比度。 病理区域和正常组织之间的磁共振图像。虽然取得了显著的进步 在过去的二十年中，在具有改进性能的造影剂的开发中， 仍然非常需要开发具有更高对比能力的造影剂 成像和靶向特定的分子实体。该项目的目标是开发一种新型的 基于蛋白质的MRI造影剂，其对不同器官具有显著改善的对比能力， 适用于各种类型的癌症和其他疾病的分子成像。 本课题的目标一是研制高弛豫率的蛋白质造影剂。目标2是测试我们的 设计的试剂在体内成像和测定体内弛豫率。此外，LD50和最大 使用小鼠确定耐受剂量。此外，为了降低免疫原性，我们将修饰蛋白质， 通过PEG化的造影剂。本文对该制剂的免疫原性、血液循环时间、稳定性及药理作用进行了研究。 将研究修饰的蛋白质。目的3是测试应用我们开发的对比度的可行性 用培养的癌细胞对疾病生物标志物进行分子成像的试剂。我们的工作是探索 克服造影剂的低灵敏度和选择性的主要限制的新机制 为各种疾病的诊断和监测治疗提供了方便。

Magnetic resonance imaging (MRI)is a powerful non-invasive tool with high spatial resolution for clinical diagnosis without the limitation of the depth of tissues. A major barrier to the application of MRI technique is its lack of sensitivity and specificity. The method routinely uses contrast agents to amplify the contrast in the magnetic resonance image between pathological regions and normal tissues. Although remarkable progress in the development of contrast agents with improved properties has been made in the last twenty years, there is still a great need for the development of contrast agents with even higher contrast capability in imaging and to target to specific molecular entities. The goal of this project is to develop a novel class of protein-based MRI contrast agents with significantly improved contrast capability for different organs and applicability in molecular imaging of various types of cancer and other diseases. In this proposal, Aim 1 is to develop the protein contrast agents with high relaxivity. Aim 2 is to test our designed agents in in vivo imaging and determine the in vivo relaxivity. In addition, LD50 and maximal tolerable doses will be determined using mice. Further, to reduce the immunogenicity, we will modify protein contrast agents by PEGylation. The immunogenesity, blood circular time, stability and pharmacology of the modified proteins will be investigated. Aim 3 is to test the feasibility of applying our developed contrast agents for molecular imaging of disease biomarkers with cultured cancer cells. Our proposed work explores a new mechanism to overcome a major limitation of low sensitivity and selectivity of contrast agents facilitating diagnosis and monitoring treatment of various diseases byMRI.