Designing Magnetic Resonance Protein-based Contrast Agents with High Relaxivity

磁共振成像(MRI)是一种强大的、无创的、高空间分辨率的临床诊断工具 诊断不受组织深度的限制。核磁共振技术应用的一个主要障碍是 它缺乏敏感性和特异性。该方法通常使用造影剂来放大 病变区与正常组织之间的磁共振图像。尽管取得了显著的进步 在具有改进性能的造影剂的发展中已经在过去的二十年中， 目前仍迫切需要开发具有更高对比度的造影剂。 成像和靶向特定的分子实体。这个项目的目标是开发一种新型的 基于蛋白质的MRI造影剂可显著提高不同器官和 适用于各种癌症和其他疾病的分子成像。 在这个方案中，目标1是开发高弛豫度的蛋白质造影剂。目标2是测试我们的 设计了体内显像剂，并测定了体内弛豫度。此外，LD50和最大 可以耐受的剂量将通过小鼠来确定。此外，为了降低免疫原性，我们将修改蛋白质 聚乙二醇化造影剂。丹参的免疫原性、血液循环时间、稳定性及药理作用 将对修饰的蛋白质进行研究。目标3是测试应用我们开发的对比度的可行性 利用培养的癌细胞对疾病生物标志物进行分子成像的试剂。我们提出的工作探索了 一种克服造影剂灵敏度和选择性低的主要缺陷的新机制 方便各种疾病的MRI诊断和监测治疗。

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.