Biodegradable polymeric iodine contrast agents for CT angiography.

描述(由申请人提供)：微型CT机器的最新进展使成像成为可能，分辨率为&lt；10？m。扫描需要大约6到20分钟才能获得，而目前的碘造影剂由于半衰期短，通常不适用。我们最近商业化了无毒的金X-射线造影剂AuroVist，但它们比碘剂贵得多，而且全身清除非常慢。现在我们提出了可生物降解的聚合物造影剂，它由FDA批准的成分组成：透明质酸或聚乳酸/聚乙交酯和碘剂碘的衍生物，比我们的 以金为基础的造影剂，比传统的碘剂更具吸收能力。新的试剂可以标记额外的造影剂，如Gd或氧化铁，从而实现多模式成像或与双束/双探测器CT进行双重对比。当标记有碘剂和靶向分子时，可以在体内可视化器官功能、血管生成、修复、肿瘤形成、转移、对药物和其他治疗或条件的反应研究，如缺血或辐射，以及动物的基本生物学研究，包括发育、感染、免疫反应、心脏研究、组织损伤和愈合。与传统的碘造影剂相比，新的造影剂将提供四倍以上的放射密度，并将使成像时间更长，因为它们是在血管内。这些试剂将通过清楚地识别脂核体积占斑块体积的百分比、血管生成/炎症和狭窄等危险因素，更准确地识别脆弱的斑块。此外，它们更高的放射密度将使肥胖患者能够更好地进行成像，减少正常大小患者的辐射剂量，并降低肾脏毒性，以便在肾脏受损的患者中使用。这些能力超过了其他药物所提供的能力，如果在临床上实施，可以通过筛查降低冠状动脉疾病死亡的患病率。

DESCRIPTION (provided by applicant): Recent advances in micro-CT machines have made it possible to image with a resolution of <10 ¿m. Scans take ~6 to 20 minutes to acquire, and current iodine contrast agents due to their short half-lives are not generally suitable. We recentl commercialized non-toxic gold X-ray contrast agent, AuroVist", but they are lot more expensive than iodine agents and their whole body clearance is very slow. We now propose biodegradable polymeric contrast agents that are composed of FDA approved components: hyaluronic acid or polylactide/polyglycolide and a derivative of iodine agent Iobitridol that are lot cheaper than our gold-based contrast agents and more absorptive than conventional iodine agents. The new agents can be labeled with additional contrast agents, such as gadolinium or iron oxide, enabling multimodal imaging or double contrasting with dual-beam/dual-detector CT. When labeled with iodine agents and targeting molecules will enable in vivo visualization of organ function, angiogenesis, repair, tumor formation, metastasis, studies of response to drugs and other therapies or conditions, such as ischemia or radiation, and basic biological studies of animals including development, infection, immune response, cardiac studies, tissue injury and healing. The new contrast agents will provide more than four times the radiodensity as compared to the conventional iodine contrast agents and will enable longer imaging times as they are intravascular. These agents will more accurately identify vulnerable plaque by clearly identifying lipid core volume as a percentage of plaque volume, angiogenesis/inflammation, and stenoses, among other risk factors. In addition, their higher radiodensity will enable better imaging of obese patients, reduce radiation dose in normal sized patients and reduce nephrotoxicity to permit use in kidney compromised patients. These capabilities go beyond what other agents offer and if clinically implemented could, through screening, reduce the prevalence of coronary artery disease deaths.