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主要的死亡原因，每年夺走约1800万人的生命。拟议的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，还显示出改善的安全性。因此，它有可能极大地改善主动脉、外周动脉、肾动脉和颈动脉等中的异常（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，这些机构执行MRA以诊断深静脉血栓形成、血管畸形、外周动脉疾病和儿科成像。这项小企业技术转让（STTR）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的长期副作用风险。对比增强MRA是血管成像的主要诊断程序，由于其出色的纵向（T1）缩短效应，目前市场主要由钆基造影剂（GBCA）主导。然而，GBCA与许多副作用和脑中的长期钆沉积有关。由于其潜在的毒性，GBCA被设计为通过肾脏过滤快速清除-仅留下用于MRA图像采集的短窗口，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），从而延长成像窗口以改善MRA中的血管成像，但随后通过肾脏过滤清除（最大限度地减少组织积聚）。第一阶段目标的成功实现将证明拟议药物实现了通过肾脏过滤清除的所需BPCA，控制药代动力学和生物分布，并证明MRA性能优于GBCA。该奖项反映了NSF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.