Slow Clearance Gadolinium-Based Extracellular and Intravascular Contrast Media for Three-Dimensional MR Angiography

The objective of this study was to assess two new slow-clearance contrast media with extracellular and intravascular distribution for magnetic resonance angiography (MRA). Extracellular Gd-DTPA-BC2glucA and intravascular Gd(DO3A)3-lys16 were developed within the European Biomed2 MACE Program and compared with two reference compounds, intravascular CMD-A2-Gd-DOTA and extracellular GdDOTA, in 12 rats. Pre- and post-contrast three-dimensional MR (TR/TE = 5 msec/2.2 msec; isotropic voxel size 0.86 mm3) was acquired for 2 hours. Signal-to-noise enhancement (ΔSNR) was calculated. Two minutes after injection, all contrast media provided strong vascular signal enhancement. The ΔSNR for Gd-DTPA-BC2glucA, Gd(DO3A)3-lys16, CMD-A2-Gd-DOTA, and GdDOTA were 13.0 ± 1.8, 25.0 ± 3.2, 25.0 ± 4.0, and 18.0 ± 3.4, respectively. Gd-DTPA-BC2glucA, Gd(DO3A)3-lys16, and CMD-A2-Gd-DOTA cleared slowly from the circulation, whereas GdDOTA cleared rapidly. Vascular ΔSNR at 2 hours were 2.9 ± 0.6, 25.0 ± 3.2, 25.0 ± 4.0, and 0.4 ± 1.0. Gd(DO3A)3-lys16 provided strong vascular and minor background enhancement, and thus may be useful for MRA or perfusion imaging. Gd-DTPA-BC2glucA produces persistent enhancement of extracellular water, and thus may allow quantification of extracellular distribution volume and assessment of myocardial viability.