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

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.