Novel Targeted Iodinated Microbubbles for Molecular Imaging With Computed Tomography

项目摘要 精准医疗为每个人提供个性化的疾病治疗和预防策略。分子 成像（MI）在精准医学中起着关键作用，因为它可以可视化生物学过程， 疾病的发展对每个人来说都是独一无二的。MI需要一个成像探头， 比如血管生成和炎症，并报告体内活动的位置。当前临床前 （超声）和临床（正电子发射断层扫描）MI应用具有有限的身体检查的缺点。 覆盖范围和空间分辨率差。计算机断层扫描（CT）产生高分辨率的3- 三维全身图像，但落后于其他MI模式，因为它缺乏临床可行的 有针对性的成像探头。这项研究的长期目标是适应和加强现有的，现成的 通过引入靶向疾病的成像探针， 可被X射线探测到。该项目的具体目标有两个方面。第一个目标是开发一种新型CT分子 结合超声中使用的靶向微泡造影剂的既定平台的成像剂 与不透射线的聚酯合成一个独特的，脂肪族，碘化单体可检测的CT，以产生 靶向碘化微泡（TIMb）。将评价TIMbs与碘的放射性造影特性 负载、温度和浓度。第二个目的是在体内模型中测试TIMb和CT参数 并比较超声心肌梗死的敏感性。该项目的成果将是TIMb，一个有针对性的 CT造影剂，可作为早期发现的工具，从根本上改善治疗 和预防疾病。这是建立CT作为临床可行的分子生物学检查的第一步。 成像，以促进高分辨率的全身分子成像所需的推动精确医学。

PROJECT SUMMARY Precision medicine individualizes disease treatment and prevention strategies for each person. Molecular imaging (MI) plays a key role in precision medicine because it visualizes the biological processes underlying the development of disease that are unique to each individual. MI requires an imaging probe that targets processes like angiogenesis and inflammation and reports the location of the activity inside the body. Current preclinical (ultrasound) and clinical (positron emission tomography) MI applications have the drawbacks of limited body coverage and poor spatial resolution, respectively. Computed tomography (CT) produces high-resolution 3- dimensional whole body images but has fallen behind other MI modalities because it lacks a clinically viable targeted imaging probe. The long-term goal of this research is to adapt and enhance an existing, readily available imaging modality, CT, for clinical molecular imaging by introducing an imaging probe that targets disease and is detectable by x-ray. The specific aims of this project are 2-fold. The first aim is to develop a novel CT molecular imaging agent by combining the established platform of targeted microbubble contrast agents used in ultrasound with radiopaque polyesters synthesized with a unique, aliphatic, iodinated monomer detectable by CT to produce targeted iodinated microbubble (TIMb). The radio-contrast properties of TIMbs will be evaluated versus iodine loading, temperature and concentration. The second aim is to test TIMb and CT parameters in an in vivo model of angiogenesis and compare sensitivity to ultrasound MI. The outcome of this project will be TIMb, a targeted contrast agent for CT, which can be used as a tool for early detection, fundamentally improving the treatment and prevention of disease. This is the first step toward establishing CT as a clinically viable option for molecular imaging to facilitate high-resolution whole body molecular imaging needed in the push toward precision medicine.