Arteriosclerosis is the major cause of human death and a primary concern for healthcare providers worldwide. Currently, the gold standard for many manifestations of vascular disease, especially arterial occlusive disease, is x-ray angiography, an invasive, costly, and potentially hazardous procedure. In the United States alone, an estimated 3.3 million diagnostic x-ray angiograms are performed annually at a cost to the healthcare system of over 6 billion dollars. Magnetic resonance angiography (MRA) offers a noninvasive and potentially less costly alternative. The availability of an effective intravascular contrast agent that can simplify data acquistion and image interpretation of MRA procedures could propel wider utilization of this diagnostic tool. Our Fast Track SBIR application will evaluate a gadolinium-based contrast reagent that is ideally suited for MRA. The formulation of this reagent is based on a novel chemical procedure for the production of stable lanthanide oxide colloids. Preliminary data demonstrates that the gadolinium oxide colloid is stable in an aqueous suspension under a variety of challenges, including autoclaving, and demonstrates that this reagent provides a strong T1 brightening signal comparable to the same molar concentration of gadolinium-DTPA. The synthetic process yields a gadolinium oxide core that is tightly bound to an inert matrix, which should afford a toxicity profile comparable to chelated gadolinium. Phase I study will focus on toxicology, biodistribution, and in vivo stability, as well as further characterize the reagent. If Phase I research is successful, Phase II research will expand toxicity evaluation in a non-rodent model as required for IND filing with the FDA and will perform efficacy studies to evaluate our MRA reagent using an in vivo swine model of myocardial ischemia and reperfusion.
