Immune-Shielded, Ultrasound-Stimulated Contrast Agents for Molecular Imaging

描述（由申请人提供）：许多有前景的研究表明，超声分子成像可以快速、经济地提供敏感、高分辨率的血管事件检测，如血管生成、炎症和血栓。因此，超声分子成像有可能在临床医学和生物学研究中产生广泛的影响。目前的非对比辅助超声缺乏特异性来检测靶向疾病事件的分子特征，如血管生成。而超声具有成本低、便携、动态成像等优点，已广泛应用于临床诊断。靶向造影剂已被开发用于超声分子成像，但其免疫原性使其无法应用于临床。因此，提高超声分子成像的安全性和灵敏度，将对血栓、炎症、癌症的诊断和评估产生重要影响。在超声分子成像应用于临床之前，必须降低造影剂表面靶向配体暴露引起的免疫原性效应。我们建议进行研究，以详细检查超声造影剂免疫反应的物理化学机制，我们将利用这些数据来设计屏蔽这种免疫反应的造影剂。同时，我们将研究超声与隐身剂的相互作用，这些隐身剂在初步数据中显示可以被超声辐射力选择性激活。与超声设备制造商的合作将允许对小动物成像系统进行特定优化的修改，以配合新的隐形造影剂增强临床前成像。最终目标将是开发更安全的超声造影剂，也将表现出更高的特异性和体内循环时间，并改进超声扫描仪技术，以利用新的隐形造影剂。公共卫生相关性：超声分子成像在临床医学和生物学研究中具有广泛影响的潜力。在超声分子成像应用于临床之前，必须降低造影剂表面靶向配体暴露引起的免疫原性效应。该项目将开发更安全的靶向超声造影剂，降低免疫原性，提高体内特异性，并改进超声扫描技术，以利用新的造影剂。

DESCRIPTION (provided by applicant): Many promising studies indicate that molecular imaging with ultrasound can rapidly and economically provide sensitive, high-resolution detection of vascular events, such as angiogenesis, inflammation and thrombus. Thus, Ultrasound molecular imaging has the potential to have a widespread impact in clinical medicine and biological research. Current non-contrast-assisted ultrasound lacks the specificity to detect molecular signatures of targeted disease events, such as angiogenesis. However, ultrasound has the advantages of low cost, portability, and dynamic imaging capability, and is already widely used for clinical diagnosis. Targeted contrast agents have been developed for ultrasound molecular imaging, but their immunogenic properties make them untranslatable to the clinic. Thus, improving the safety and enhancing the sensitivity of ultrasound molecular imaging will have a significant impact on the diagnosis and assessment of thrombus, inflammation, and cancer. Before ultrasound molecular imaging can be translated to the clinic, the immunogenic effects caused by the exposure of targeting ligands on the contrast agent surface must be reduced. We propose research studies to examine in detail the physicochemical mechanisms of immune response to ultrasound contrast agents, and we will use this data to design contrast agents which are shielded from this immune response. Simultaneously, we will study the ultrasound interaction with stealth agents that have been shown in preliminary data to be selectively activated by ultrasound radiation force. Collaboration with an ultrasound device manufacturer will allow the modification of a small-animal imaging system for specific optimization to work with the new stealth contrast agents for enhanced pre-clinical imaging. The end goal will be to develop safer ultrasound contrast agents which will also exhibit increased specificity and circulation time in-vivo, and to improve ultrasound scanner technology to take advantage of new, stealth contrast agents. PUBLIC HEALTH RELEVANCE: Ultrasound molecular imaging has the potential to have a widespread impact in clinical medicine and biological research. Before ultrasound molecular imaging can be translated to the clinic, the immunogenic effects caused by the exposure of targeting ligands on the contrast agent surface must be reduced. The project will develop safer targeted ultrasound contrast agents with decreased immunogenicity and increased specificity in vivo and improve ultrasound scanner technology to take advantage of the new contrast agents.