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Superparamagnetic iron oxide (ferrite) particles were evaluated as a contrast agent for magnetic resonance (MR) imaging. In this pilot study, doses ranging from 10 to 50 mumol/kg were administered intravenously to 15 patients. Ferrite-enhanced images of the liver obtained with standard pulse sequence techniques significantly increased the number of hepatic lesions detected (P less than .01) and reduced the threshold size for detection to 3 mm (P less than .01). The improved clinical performance of ferrite-enhanced images correlated with significant increases in measured contrast-to-noise ratios (P less than .01). Degradation of superparamagnetic activity and/or clearance of ferrite from the liver was demonstrated as early as 12 hours after injection, suggesting that the lack of chronic toxicity observed in animal studies may be reproduced in humans. These initial clinical results appear to confirm extensive preclinical data indicating that ferrite administered at a dose of 20 mumol/kg has the potential to significantly improve the performance of abdominal MR imaging.

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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).

Relations between spatial distribution of superparamagnetic iron oxide (SPIO) particles and the image contrast caused by SPIO were investigated. Actual clustering pattern of particles was measured in the liver and spleen of animals using intravital laser confocal microscopy. SPIOdoped phantoms with and without Sephadex beads were made to simulate these patterns, and relaxation parameters were measured using a 1.5-T clinical scanner. Finally, these results were compared to clinical image data using SPIO particulate agent. Intravital microscopy indicated that the clustering of latex beads was more predominant in hepatic Kupffer cells than in splenic macrophages (P < 0