Albumin-Targeted MRI Agents for Tumor Detection

Metasyn, Inc. is developing a high-efficiency contrast agent for magnetic resonance imaging(MRI) to improve the detection of brain and spine tumors. Current MRI agents are small molecular weightgadolinium(III) chelates which have limited water proton relaxation ability (relativity) and thus, in certaincircumstances, limited MRI enhancement capability. Multiple doses are often used, at high cost (app.$250), to insure detection of small lesions. Metasyn is planning to compete with these products withan agent with much higher relativity and the same cost as a single dose of the conventional agents (app.$85). In addition, it is anticipated that a high-efficiency agent would lead to a longer window ofenhancement which is in demand for use in lengthy MRI exams. The overall goal is to test the feasibilityof certain gadolinium(III) chelates which bind reversibly to human serum albumin (HSA) in blood andtissues. The increase in the rotational tumbling time of the chelate leads to increased relativity. A seriesof chelates will be synthesized and tested for relativity, HSA binding ability, and biodistribution in rats(including blood clearance rates). Structure-activity relationships will be determined as a function of thelipophilicity of the chelates. The tumor MRI enhancement capability for the agents with the highestrelativity and blood concentration will be evaluated in a rat tumor model (mammary adenocarcinomaR3230AC) and compared to conventional agents. Selected agents will undergo further testing in PhaseII which will include formal pharmacokinetic and toxicological studies, investigational new drug (IND)application submission, and Phase I clinical trials.