Novel tungsten and bismuth nanoparticle contrast agents for MicroCT.

描述（由申请人提供）：微型CT机的最新进展使得能够以<10 μ m的分辨率成像。扫描需要约6至20分钟来采集，并且目前的碘造影剂由于其半衰期短而通常不适合。我们最近 商品化的金X射线造影剂AuroVist”，但它们比碘剂更昂贵。我们现在建议开发基于钨和铋的重金属纳米颗粒造影剂，其比我们的基于金的造影剂便宜得多，并且比碘更具吸收性。新试剂可以用反应性基团官能化以共价交联至靶向分子，并且将使得能够在体内可视化器官功能、血管生成、修复、肿瘤形成、转移、对药物和其它治疗或病症（例如局部缺血或辐射）的响应的研究以及动物的基础生物学研究，包括发育、感染、免疫应答、心脏研究、组织损伤和愈合。 碘化造影剂在许多患者中引起造影剂诱导反应（CIR），包括过敏、哮喘、肾病和糖尿病患者。对于肾脏受损的患者，CIR可能会产生严重的后果。CIR归因于碘剂的高粘度和渗透压摩尔浓度。所提出的对重金属试剂的新型表面改性将改善其粘度。与< 5.5 nm hydrodynamic diameter can hold >3或6个碘原子相比，每个颗粒具有250个金属原子的较小的钨和铋纳米颗粒;它们将具有低得多的渗透压并产生更高的对比度，并有助于缓解与对比剂诱导的肾病相关的问题。 最后，由于钨（69.52 keV）和铋（90.5 keV）的K边缘与碘（33.12 keV）很好地分离，因此双能量（双束/双探测器）CT可以同时进行双对比（碘和钨/或铋的“K边缘成像”）。 公共卫生相关性：所提出的用于体内microCT X射线成像的新型无毒钨和铋造影剂具有比碘剂更高的衰减系数，并且将减少数百万患者的X射线剂量，并且当与碘剂一起使用时，将能够利用双能量CT同时对两个目标进行成像。

DESCRIPTION (provided by applicant): Recent advances in microCT 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 life are not generally suitable. We recently commercialized gold X-ray contrast agent, AuroVist", but they are more expensive than iodine agents. We now propose to develop heavy metal nanoparticle contrast agents based on tungsten and bismuth that are lot cheaper than our gold-based contrast agents and more absorptive than iodine. The new agents can be functionalized with reactive groups for covalent cross-linking to targeting molecules and 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 iodinated contrast agents cause contrast induced reactions (CIRs) in many patients, including those with allergies, asthma, kidney diseases and diabetes. For patients with compromised kidneys the CIRs can have serious consequences. The CIRs are attributed to the high viscosity and osmolality of the iodine agents. The proposed novel surface modifications to the heavy metal agents will improve their viscosities. The smaller tungsten and bismuth nanoparticles with < 5.5 nm hydrodynamic diameter can hold >250 metal atoms per particles as compared to 3 or 6 iodine atoms; they will have much lower osmolality and produce higher contrast, and help alleviate problems related to contrast induced nephropathy. Finally, because the K-edges of tungsten (69.52 keV) and bismuth (90.5 keV) are well separated from iodine (33.12 keV), simultaneous double contrasting ("K-edge imaging" with iodine and tungsten/or bismuth) will be possible with dual-energy (dual-beam/dual-detector) CT. PUBLIC HEALTH RELEVANCE: The proposed novel non-toxic tungsten and bismuth contrast agents for in vivo microCT X-ray imaging have higher attenuation coefficients than iodine agents and will reduce X-ray dose to millions of patents, and when used with iodine agents will enable simultaneous imaging of two targets with dual-energy CT.