Pharmacokinetics and enhancement patterns of macromolecular MR contrast agents with various sizes of polyamidoamine dendrimer cores

Four macromolecular contrast agents are synthesized to visualize small vess els by MRI using generation-3 (G3D), -4 (G4D), -5 (G5D), and -6 (G6D) polya midoamine dendrimers conjugated to chelated gadolinium (Gd). The pharmacoki netics, enhancement patterns, and the ability of these constructs to visual ize fine vessels is evaluated by dynamic MRI in relationship to their size. Gd-G6D and -G5D exhibit a prolonged high vascular (ventricular) signal int ensity (SI) with high ventricle-to-organ SI ratios. The initial high vascul ar SI with Gd-G4D decreases to a value as low as that obtained with Gid-G3D and Gd-dimeglumine-diethylenetriaminepentaacetic acid (Gd-DTPA). Gd-G5D, - G4D, and -G3D show high renal Isis, and Gd-DTPA prominently enhances the sk in. Gd-G6D and -G5D present fine vasculature significantly more clearly tha n Gd-G3D and -DTPA (P < 0.005). As the molecular size increases, the excret ion of the Gd-153-conjugates is retarded. In conclusion, Gd-G6D and -G5D ar e retained in the blood and present fine vessels with high quality and deta il, and should be adequate for visualizing small tumor vasculature. (C) 200 1 Wiley-Liss, Inc.