Development of MB-102 as fluorescent tracer for ocular angiography

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PROJECT SUMMARY/ABSTRACT Fluorescent angiography is a commonly used diagnostic tool for visualizing eye vasculature when a physician suspects a patient suffers from retinal vascular diseases such as diabetic retinopathy and age-related macular degeneration. To visualize eye vasculature, the fluorescent dye fluorescein is injected intravenously. Administration of fluorescein is associated with both mild and severe adverse reactions. Mild reactions such as nausea, vomiting, and pain at the injection site are frequent and likely associated with the need to dissolve fluorescein in alkaline solutions. More severe reactions, such as allergic reactions, seizures, and death are less frequent but limit ocular angiography use since a crash cart must be present during fluorescein administration. MediBeacon has developed a second-generation IV fluorescent dye (MB-102) with several advantages over fluorescein. MB-102 is soluble at physiological pH and therefore does not require alkaline dissolution. Also, there is no known metabolism of MB-102 in humans, suggesting that the likelihood of an anaphylactic response will be considerably lower than for fluorescein. We have preliminary proof of concept data from mice showing that MB-102 can be used to visualize ocular vasculature. MB-102 has undergone full preclinical toxicology and was found safe in a 32-subject Phase I human study for another indication. This SBIR will assess the use of MB-102 for visualizing ocular vasculature in healthy dogs and dogs with either hypertensive or diabetic retinopathy. The first specific aim of this project is to establish a standardized protocol for MB-102 administration and compare the quality of images obtained with MB-102 to images obtained using standard fluorescein angiography. As part of this aim we will first optimize the imaging setup for detection of MB-102 and then establish the optimal MB-102 dose for performing anterior and posterior segment angiography in healthy dogs. The second specific aim of this project tests MB-102 in dogs suffering from hypertensive or diabetic retinopathy. This aim is to compare and contrast the diagnostic capabilities of MB-102 to standard fluorescein imaging. The goal of this project is to prove that MB-102 can provide the same diagnostic information as fluorescein in eye vasculature diseases. According to our internal analysis, fluorescein is a $225 million annual market served by a number of generic pharmaceutical companies. A superior proprietary reagent with an improved safety profile and better diagnostic utility should lead to significant market adoption.