3D‐micro‐MR angiography of mice using macromolecular MR contrast agents with polyamidoamine dendrimer core with reference to their pharmacokinetic properties

Four novel macromolecular MRI contrast agents, all of which had the same chemical composition but different molecular weights, were prepared using generation‐3, ‐4, ‐5, and ‐6 polyamidoamine (PAMAMTM) dendrimers conjugated with a bifunctional diethylenetriaminepentaacetic acid derivative to change the blood retention, tissue perfusion, and excretion. Size‐dependent changes in the pharmacokinetics were observed in the biodistribution study. 153Gd‐labeled generation‐6 PAMAMTM‐conjugates remained in the blood significantly longer than all of the other preparations (P < 0.001). The increase in blood‐to‐organ ratio of the preparations was found to correlate with increasing molecular size (P < 0.001). Additionally, 3D‐micro MR images and angiography of mice of high quality and detail were obtained using PAMAMTM‐(1B4M‐Gd)x as a macro‐molecular MRI contrast agent with a 1.5‐T clinical MRI instrument. Numerous fine vessels of ∼200 μm diameter were visualized on subtracted 3D‐MR angiographms with G6D‐(1B4M‐Gd)192. The quality of the images was sufficient to estimate the microvasculature of cancerous tissue for anti‐angiogenesis therapy and to investigate knockout mice. Magn Reson Med 45:454–460, 2001. © 2001 Wiley‐Liss, Inc.