Magnetic resonance angiography

描述（由申请人提供）：动脉炎是人类死亡的主要原因，也是全球医疗保健提供者的主要关注点。目前，血管疾病，特别是动脉闭塞性疾病的许多表现的金标准是X射线血管造影术，这是一种侵入性的、昂贵的和潜在危险的程序。仅在美国，估计每年进行330万次诊断X射线血管造影，医疗保健系统的成本超过60亿美元。磁共振血管造影（MRA）提供了一种非侵入性和潜在的成本较低的替代方案。一种有效的血管内造影剂的可用性，可以简化数据采集和图像解释的MRA程序，可以推动更广泛地利用这种诊断工具。我们的Fast Track SBIR应用程序将评估一种非常适合MRA的钆基造影剂。该试剂的配方基于一种用于生产稳定的镧系氧化物胶体的新型化学程序。初步数据表明，氧化钆胶体在各种挑战下（包括高压灭菌）在水性悬浮液中是稳定的，并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。合成过程产生紧密结合到惰性基质的氧化钆核，其应提供与螯合钆相当的毒性特征。I期研究将重点关注毒理学、生物分布和体内稳定性，并进一步表征试剂。如果I期研究成功，II期研究将根据向FDA提交IND申请的要求，在非啮齿类动物模型中扩大毒性评价，并将使用猪心肌缺血和再灌注的体内模型进行疗效研究，以评价我们的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.