Molecular MR Imaging by Targeting Cancer Markers

描述（申请人提供）：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，不受组织深度的限制，可用于临床诊断。MRI技术应用的一个主要障碍是它的低灵敏度和特异性。造影剂通常用于增强病变区域和正常组织之间的图像对比度。我们已经开发了一种新型的MRI造影剂，与常用的造影剂相比，它提供了十倍以上的对比度增强。为了响应体内癌症成像（PA-06371）的研究提案，我们建议开发一类新的基于蛋白质的MRI造影剂，以实现癌症标志物HER-2的磁共振成像。我们将利用我们开发的蛋白质造影剂作为基础，融合靶向HER-2的靶向肽。目的1是设计和表征蛋白质造影剂，并测试培养癌细胞的分子磁共振成像。目的2是通过分子标记介导的识别对荷瘤小鼠的肿瘤进行成像。我们提出的工作探索了一种新的机制，通过蛋白质设计来克服当前MRI方法的低灵敏度和特异性。所开发的灵敏的非侵入性诊断成像方法将对非裔美国人癌症患者的诊断、监测癌症进展和治疗产生重大影响。我们研究的成功也将为研究HER-2在促进癌症进展中的生物学作用提供一个通用的工具。这项研究也可能有助于减少癌症死亡的种族差异。

DESCRIPTION (provided by applicant): 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 low sensitivity and specificity. Contrast agents are routinely used to amplify the image contrast between disease regions and normal tissues. We have developed a novel class of MRI contrast agent that provide over ten fold higher contrast enhancement compared to that of commonly used contrast agent. In response to the call for research proposals for in vivo cancer imaging (PA-06371), we propose to develop a novel class of protein-based MRI contrast agents to enable magnetic resonance imaging of cancer markers HER-2. We will ultilize our developed protein contrast agent as base to fuse a targeting peptide that target HER-2. Aim 1 is to design and characterize protein contrast agents and to test for molecular MR imaging with cultured cancer cells. Aim 2 is to image cancers in tumor bearing mice via molecular marker-mediated recognition. Our proposed work explores a new mechanism to overcome the low sensitivity and specificity of current MRI methods by protein design. The developed sensitive non-invasive diagnostic imaging method will have a significant impact in diagnosis, monitoring cancer progression, and treatment of African-American cancer patients. Success in our research will also provide a versatile tool to study the biological role of HER-2 in promoting cancer progression. This study will also potentially help to reduce the ethnic differences in the cancer death.