Advanced Manufacturing Process for High Performance MRI Contrast Agents

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DESCRIPTION (provided by applicant): Contrast-enhanced magnetic resonance imaging is widely used for non-invasive diagnosis of a variety of diseases. However due to the intrinsic properties of existing gadolinium-chelate contrast agents, there exist clinical needs of improved MRI contrast agents that render extended circulatory half-life enabling blood pool imaging with favorable biodistribution and enabling tissue-specific imaging; reduce Gd associated long term safety concerns; have greater relaxivity and generate positive contrast enhancement. Luna is developing metallofullerene-based T1 agents for both blood pool imaging and targeted imaging of cancer and atherosclerotic plaque. We have conducted extensive animal studies demonstrating substantially improved imaging sensitivity at lower does, and no acute toxicity was found. It is a very promising new T1 contrast agent platform technology. However, to be cost competitive and capable of producing clinically relevant quantities, it is necessary to improve the existing manufacturing process for metallofullerenes. Luna proposes to develop a high-volume train sublimation process in place of the existing batch extraction-purification processes allowing direct collection of high purity metallofullerenes from as-produced reactor soot. Fundamental improvements will be made in existing manufacturing processes that deliver substantial productivity, quality, and environmental benefits. These improvements will overcome challenges facing the high cost purification, a significant barrier in the realization of metallofullerene-based MRI contrast agents. In vitro testing will be conducted following the proposed production process to demonstrate that the physiochemical and magnetic properties are not affected. We will also extrapolate information from the structure-activity (relaxivity) relationship and optimize the relaxivity property to maximize the clinical potential of our Hydrochalarone agents. Along with stability studies and quality control assays, the Phase I results will provide a sound foundation to proceed to Phase II for IND- enabling pharmacokinetics, toxicity and imaging studies.