Magnetic resonance angiography

描述(由申请人提供)：动脉硬化是人类死亡的主要原因，也是世界各地医疗保健提供者的主要担忧。目前，许多血管疾病，特别是动脉闭塞性疾病的黄金标准是x射线血管造影术，这是一种侵入性的、昂贵的、潜在的危险程序。仅在美国，估计每年就有330万次诊断性X射线血管造影术，医疗保健系统的成本超过60亿美元。磁共振血管成像(MRA)提供了一种非侵入性的、可能成本更低的替代方法。一种有效的血管内造影剂可以简化MRA过程的数据采集和图像解释，这可能会推动这种诊断工具的更广泛应用。我们的Fast Track SBIR应用程序将评估一种非常适合MRA的格拉基造影剂。该试剂的配方是基于一种用于生产稳定的稀土氧化物胶体的新的化学程序。初步数据表明，氧化钆胶体在包括高压灭菌在内的各种挑战下在水悬浮液中是稳定的，并证明该试剂提供了与相同摩尔浓度的Gd-DTPA相当的强烈的T1增亮信号。该合成过程产生了与惰性基质紧密结合的氧化格拉核，其毒性分布应可与螯合Gd相媲美。第一阶段的研究将集中在毒理学、生物分布和体内稳定性，以及进一步表征试剂。如果第一阶段研究成功，第二阶段研究将按照向FDA提交IND文件的要求，扩大在非啮齿动物模型中的毒性评估，并将进行有效性研究，以使用活体猪心肌缺血和再灌注模型来评估我们的MRA试剂。

DESCRIPTION (provided by applicant): Arteriosclerosis is the major cause of human death and a primary concern for healthcare providers worldwide. Currently, the gold standard for many manifestations of vascular disease, especially arterial occlusive disease, is x-ray angiography, an invasive, costly, and potentially hazardous procedure. In the United States alone, an estimated 3.3 million diagnostic x-ray angiograms are performed annually at a cost to the healthcare system of over 6 billion dollars. Magnetic resonance angiography (MRA) offers a noninvasive and potentially less costly alternative. The availability of an effective intravascular contrast agent that can simplify data acquistion and image interpretation of MRA procedures could propel wider utilization of this diagnostic tool. Our Fast Track SBIR application will evaluate a gadolinium-based contrast reagent that is ideally suited for MRA. The formulation of this reagent is based on a novel chemical procedure for the production of stable lanthanide oxide colloids. Preliminary data demonstrates that the gadolinium oxide colloid is stable in an aqueous suspension under a variety of challenges, including autoclaving, and demonstrates that this reagent provides a strong T1 brightening signal comparable to the same molar concentration of gadolinium-DTPA. The synthetic process yields a gadolinium oxide core that is tightly bound to an inert matrix, which should afford a toxicity profile comparable to chelated gadolinium. Phase I study will focus on toxicology, biodistribution, and in vivo stability, as well as further characterize the reagent. If Phase I research is successful, Phase II research will expand toxicity evaluation in a non-rodent model as required for IND filing with the FDA and will perform efficacy studies to evaluate our MRA reagent using an in vivo swine model of myocardial ischemia and reperfusion.