STTR Phase I: Novel size-changing, gadolinium-free contrast agent for magnetic resonance angiography

这项小企业技术转让（STTR）第一阶段项目的更广泛影响/商业潜力是改善心血管疾病的诊断，心血管疾病是全球最大的死亡原因，每年夺去约1800万人的生命。这项工作将开发一种造影剂，通过增强血管系统的图像来提高磁共振血管造影（MRA）的诊断价值，并且与目前使用的造影剂相比，它也显示出更高的安全性。因此，它有可能极大地提高对主动脉、外周动脉、肾动脉和颈动脉等动脉异常（如动脉瘤）的检测。该产品将为开展mra诊断深静脉血栓形成、血管畸形、外周动脉疾病和儿童影像学的放射科医师和医疗机构带来重要价值。这项小型企业技术转移（STTR）的第一阶段将开发一种新型的铁基血池造影剂（BPCA），用于磁共振血管造影（MRA），具有增强的成像能力和降低长期副作用的风险。对比增强MRA是血管成像的主要诊断方法，目前市场主要由钆基对比剂（gbca）主导，因为它们具有优异的纵向（T1）缩短效果。然而，gbca与许多副作用和脑内长期钆沉积有关。由于其潜在的毒性，gbca被设计为通过肾脏过滤迅速清除-只留下一个短窗口的MRA图像采集，导致图像质量差。为了满足对提供增强血管成像的更安全造影剂的需求，该项目将开发一种基于铁的BPCA（即保留在血管中的BPCA），从而延长MRA中血管成像的成像窗口，但随后通过肾脏过滤清除（最大限度地减少组织积聚）。I期目标的成功实现将证明所提议的药物达到所需的BPCA，通过肾脏过滤清除，控制药代动力学和生物分布，并显示出与gbca相比增强的MRA性能。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is improved diagnosis of cardiovascular disease, the top cause of death globally, taking about 18 million lives each year. The proposed work will develop a contrast agent that improves the diagnostic value of magnetic resonance angiograms (MRA), by enhancing images of the vascular system, and which also shows an improved safety profile compared to currently utilized contrast agents. It thus has the potential to vastly improve the detection of abnormalities (e.g. aneurysms) in the aorta, peripheral, renal, and carotid arteries, among others. This product will bring significant value to radiologists and medical institutions that perform MRAs for diagnosis of deep venous thrombosis, vascular malformations, peripheral arterial disease, and in pediatric imaging. This Small Business Technology Transfer (STTR) Phase I will develop a novel iron-based, blood-pool contrast agent (BPCA) for use in magnetic resonance angiograms (MRA) with enhanced imaging capabilities and reduced risk of long-term side effects. Contrast-enhanced MRA is a staple diagnostic procedure for imaging blood vessels, and the market is currently dominated by gadolinium-based contrast agents (GBCAs) due to their excellent longitudinal (T1)-shortening effects. However, GBCAs are associated with numerous side effects and long-term gadolinium deposition in the brain. Due to their potential toxicity, GBCAs are designed to be rapidly cleared through kidney filtration – leaving only a short window for MRA image acquisition and resulting in poor image quality. To address the need for a safer contrast agent that provides enhanced vascular imaging, this project will develop an iron-based BPCA (i.e. one that remains in blood vessels), enabling an extended imaging window for improved vascular imaging in MRA, but which is then cleared by kidney filtration (minimizing tissue accumulation). Successful accomplishment of Phase I goals will demonstrate that the proposed agent achieves the desired BPCA that is cleared through kidney filtration, control pharmacokinetics and biodistribution, and demonstrates enhanced MRA performance versus GBCAs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.