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

STTR 第一阶段：用于磁共振血管造影的新型尺寸变化、无钆造影剂

• 批准号: 2052242
• 负责人: Abhinav Sannidhi
• 金额: $ 25.6万
• 依托单位: NANOXORT LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2052242&HistoricalAwards=false
• 关键词: STTR; Phase; Novel; size; changing

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.

该小型企业技术转移（STTR）项目的更广泛的影响/商业潜力改进了心血管疾病的诊断，这是全球死亡的主要原因，每年大约需要1800万人生命。提出的工作将开发一种对比剂，该对比剂通过增强血管系统的图像来改善磁共振血管造影（MRA）的诊断值，并且与当前使用的对比剂相比，这也显示出改善的安全性。因此，它有可能大大改善主动脉，外周，肾脏和颈动脉等异常（例如动脉瘤）的检测。该产品将为放射科医生和医疗机构带来重大价值，这些医学机构对深静脉血栓形成，血管畸形，周围动脉疾病以及小儿成像进行MRA进行MRA。这一小型企业技术转移（STTR）I期将开发一种新型的基于铁的血液对比剂（BPCA），用于磁共振血管造影（MRA），具有增强的成像能力，并降低了长期副作用的风险。对比增强的MRA是对血管进行成像的主食诊断程序，由于其出色的纵向（T1） - 静态效应，市场目前由基于Gadolinium的对比剂（GBCA）主导。然而，GBCA与大脑中的许多副作用和长期的gadolin沉积有关。由于其潜在毒性，GBCA被设计为通过肾脏过滤迅速清除 - 仅留下很短的MRA图像获取窗口，并导致图像质量差。为了满足对提供增强血管成像的更安全的对比剂的需求，该项目将开发基于铁的BPCA（即保留在血管中的BPCA），从而实现了一个扩展的成像窗口，以改善MRA中的血管成像，但随后通过肾脏过滤（最小化组织的积累）清除。成功实现第一阶段目标将证明，提议的代理实现了通过肾脏过滤，控制药代动力学和生物分配来清除所需的BPCA，并证明了MRA绩效与GBCAS相对于GBCAS的增强。该奖项反映了NSF的法定任务，并通过使用基金会的Merit进行评估，并通过评估了CRCRIT和BRODIT和BRODIT和BRODITAIL和BRODITAIL和BRODITAIL和BRODITAILATIAL和BRODITAIL和BRODITAILATIAL和BRODITIAL和BRODITAILATIAL。