A new polysaccharide macromolecular contrast agent for MR imaging: Biodistribution and imaging characteristics

The aims of this study were to characterize certain physicochemical, pharma cokinetic, and enhancement properties of a new macromolecular contrast agen t, carboxymethyl hydroxyethyl starch-(Gd-DO3A)(35) [CMHES-(Gd-DO3A)(35)], c onsisting of a polysaccharide backbone covalently derivatized with multiple macrocyclic chelating groups for gadolinium. CMHES-(Gd-DO3A)(35) has an av erage molecular weight of 72 kD and a plasma half-time of 8.4 hours. T1 and T2 relaxivities are 14.1 +/- 0.1 L mmol(-1) . sec(-1) and 17.8 +/- 0.9 L m mol(-1) . sec(-1). respectively, for each gadolinium. ion measured at 39 de greesC and 20 Mhz; this T1 relaxivity is more than 4 times that of gadopent etate. Seven days after intravenous administration only relatively small am ounts of gadolinium. could be detected in blood or other tissues of rats. T he compound was well tolerated in diagnostic dosages by all experimental an imals. Magnetic resonance angiography performed within 1 hour of CMHES-(Gd- DO3A)(35) administration showed a near-constant and strong enhancement of b lood in arteries and veins. Analysis of dynamic enhancement patterns of exp erimental tumors (MAT-LyLu prostate cancer implanted in rats) following int ravenous CHMES-(Gd-DO3A)(35) administration yielded quantitative estimates of tumor plasma volume and microvessel permeability; the demonstrated hyper permeability of tumor microvessels was easily distinguished from the absenc e of measurable microvascular permeability In non-neoplastic soft tissues. J. Magn. Reson. Imaging 2000;11:694-701. (C) 2000 Wiley-Liss, Inc.