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 ch emical composition but different molecular weights, were prepared using gen eration-3, -4, -5, and -6 polyamidoamine (PAMAM(TM)) dendrimers conjugated with a bifunctional diethylenetriaminepentaacetic acid derivative to change the blood retention, tissue perfusion, and excretion. Size-dependent chang es in the pharmacokinetics were observed in the biodistribution study. Gd-1 53-labeled generation-6 PAMAM(TM)- conjugates remained in the blood signifi cantly 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 inc reasing molecular size (P < 0.001). Additionally, 3D-micro MR images and an giography of mice of high quality and detail were obtained using PAMAM(TM)- (1B4M-Gd)x as a macro-molecular MRI contrast agent with a 1.5-T clinical MR I instrument. Numerous fine vessels of similar to 200 mum diameter were vis ualized on subtracted 3D-MR angiographms with G6D-(1B4M-Gd)(192). The quali ty of the images was sufficient to estimate the microvasculature of cancero us tissue for anti-angiogenesis therapy and to investigate knockout mice. ( C) 2001 Wiley-Liss, Inc.