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，也是全世界医疗保健提供者关注的主要问题。目前，许多血管疾病，特别是动脉闭塞性疾病的金标准是x线血管造影，这是一种侵入性的、昂贵的、潜在危险的手术。仅在美国，估计每年就有330万例诊断性x射线血管造影被执行，医疗保健系统的成本超过60亿美元。磁共振血管造影（MRA）提供了一种无创且潜在成本较低的替代方法。一种有效的血管内造影剂的可用性可以简化MRA程序的数据采集和图像解释，可以推动这种诊断工具的广泛应用。我们的快速通道SBIR应用将评估一种非常适合MRA的钆基造影剂。该试剂的配方是基于一种新的化学程序，用于生产稳定的镧系氧化物胶体。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，并且表明该试剂提供了与相同摩尔浓度的钆- dtpa相当的强T1增亮信号。该合成过程产生的氧化钆核心与惰性基质紧密结合，其毒性可与螯合钆相媲美。第一阶段的研究将侧重于毒理学、生物分布和体内稳定性，以及进一步表征试剂。如果I期研究成功，II期研究将扩大在非啮齿动物模型中的毒性评估，以满足向FDA提交IND申请的要求，并将在猪体内心肌缺血和再灌注模型中进行功效研究，以评估我们的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.