Magnetic resanance imaging (MRI) has proved to be an extremely valuable diagnostic imaging modality since its introduction as a clinical tool in the 1980s. Even though MRI inherently provides for tissue contrast, administration of exogenous MRI contrast agents has demonstrated the ability to improve the diagnostic accuracy of magnetic resonance imaging. One class of MRI contrast agents is the gadolinium-based chelates. These agents possess paramagnetic properties that enhance the rate of relaxation of hydrogennuclei in an external magnetic field. The result of the paramagnetic effect is a decrease in the T1 (spin-lattice) and T2 (spin-spin) relaxation times in tissues that contain the gadolinium complex. The ability to distinguish normal from abnormal tissue in MRI depends on the signal intensity differences between tissues which are, in part, a function of T1 and T2 relaxation times. Successful clinical utility of a MRI contrast agent generally involves certain rquirements such as: (1) magnetic activity that actually modifies signal intensity, (2) biodistribution to tissue resulting in either differential uptake or exclusive uptake by diseased tissue, and (3) low toxicity for the efficacious doses. With these rquirements in focus, Mallinckrodt Medical, Inc. has developed and is investigating Optimark (gadoversetamide injection), a nonionic, extracellular, linear goadolinium chelate for use as an intravenous MRI contrast agent. Optimark is a sterile, nonpyrogenic, 0.5 mmol/ml clear, aqueous solution. In preclinical studies, Optimark has shown biologic eztracellular fluid volume distribution with clearance similar to substances that are eliminated through glomerular filtration. In comparative preclinical studies, Optimark has demonstrated similary biodistribution, elimination, and effacacy (signal enhancement) properties to gadopentetate dimeglumine injection (Gd-DTPA). Some gadolinium-based compounds ahe demonstrated positive efficacy results at doses greater that in the current standard of 0.1 mmol/kg. Various doses (0.1 mmol/kg-0.5 mmol/kg) of Optimark are currently being investigated in numerous patient populations.
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