The founders of Marval Therapeutics have recently invented a new class of CT contrast agents that circulate in the bloodstream for extended periods of time' providing constant opacification of the blood for these extended duration These agents are based on commercially available Iodine compounds encapsulated in Stealth(R) liposome. Stealth(R) liposomes are well known to (1) remain in circulation for long periods, with a half-life of 8-24 hours, and, (2) clear from the circulation via the liver and the rest of the reticuloendothelial system. Contents of the liposomes will therefore only minimally contact the renal system. However, they will remain in the blood stream for the duration of several hours, enabling convenient, non time-constrained, cardiac imaging. Additionally, they are known to extravasate in regions of vascular damage, angiogenesis, inflammation and infection potentially enabling enhanced tumor imaging and possibly classification"""""""". In our proposed work, we focus on the cardiac imaging application alone. The availability of a liposomal CT agent such as ours, would have the combined benefit of eliminating risks of current procedures, reducing toxic side effects of current agents/administration methods, enabling imaging in currently contraindicated populations, and most importantly, enabling imaging technologies for cardiac imaging that do not exist today. Additionally, since these would all be based on the currently practiced CT angiogram, we believe their acceptance in clinical practice will be rapid. Our Phase 1 proposal (this proposal) seeks to develop the core technology to enable these exciting new imaging applications. A key shortcoming of our long circulating contrast agents in their current form is their relatively low Iodine concentrations (37 mgI/ml), necessitating an infusion of nearly 20% total blood volume (approximately 1 liter injection in a 70kg adult) to provide satisfactory conspicuity of the blood pool. Before further development of this agent can take place, the overall Iodine concentration will have to be increased at least 3-5 fold. Our Phase 2 proposal (to be submitted upon completion of phase 1) we will test our agents in CT angiography studies in animal models. The novelty and significance of this work lies in the ability to perform these studies 1) without bolus tracking or continuous infusion, (2) minimal renal load, thus reducing the risks of current imaging protocols.
