Manganese(II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis (phosphate) (MnDPDP) is a paramagnetic complex designed for use as a hepatobiliary agent. The T1 relaxivity of MnDPDP (2.8 [mmol/L]-1.sec-1 in aqueous solution) was similar to that of gadolinium diethylenetriaminepentaacetic acid (DTPA) (4.5 [mmol/L]-1.sec-1) and gadolinium tetraazocyclodecanetetraacetic acid (DOTA) (3.8 [mmol/L]-1.sec-1). However, in liver tissue the T1 relaxivity of MnDPDP (21.7 [mmol/L]-1.sec-1) was threefold higher than that reported for Gd-DOTA (6.7 [mmol/L]-1.sec-1). Maximum liver T1 relaxation enhancement occurred 30 minutes after injection of MnDPDP, at which time 54MnDPDP biodistribution studies indicated that 13% of total body activity was in the liver. Enhanced (MnDPDP, 50 mumol/kg) MR images showed a fivefold increase in tumor-liver contrast-to-noise ratio over baseline unenhanced images. Results of the authors' acute and subchronic toxicity studies suggest that MnDPDP will be safe at the doses necessary for clinical imaging; at 10 mumol/kg, the safety factor (LD50/effective dose) for MnDPDP is 540, significantly greater than the safety factor of Gd-DTPA (ie, 60-100).
At the currently administered clinical doses, paramagnetic metal chelate complexes presently used as MR contrast enhancement agents appear to be relatively nontoxic. Solution thermodynamic, solubility, and selectivity studies, based on a number of gadolinium chelate complexes, indicate that very little gadolinium is released in vivo, and the small amounts that do remain are available for excretion, albeit slowly. Although the mechanism of metal release from manganese-based chelate complexes is not well understood, any released manganese is likely to be quickly and efficiently cleared through the liver. Although MRI contrast agents are unlikely to be administered repeatedly in patients, which could result in accumulation of metal ion, the long-term effects of such potential deposition have yet to be demonstrated.
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