Two novel macromolecular MRI contrast agents based upon generation-6 polyamidoamine dendrimers (G6) of presumed similar molecular size, but of different molecular weight, were compared in terms of their blood retention, tissue distribution, and renal excretion. Two G6s with either ammonia core (G6A) or with ethylenediamine core (G6E), which possessed 192 and 256 exterior primary amino groups, respectively, were used. These dendrimers were reacted with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). The G6-1B4M conjugates were reacted with 153Gd for studying biodistribution and blood clearance or Gd(III) for the MRI study. 3D-micro-MR angiography of the mice were taken with injection of 0.033 mmol of Gd/kg of G6A-(1B4M-Gd)192 or G6E-(1B4M-Gd)256 using a 1.5-T superconductive MRI unit. Although numerous fine vessels of ∼100 μm diameter were visualized on subtracted 3D-MR-angiography with both G6A-(1B4M-Gd)192 and G6E-(1B4M-Gd)256, 153Gd-labeled saturated G6E-(1B4M)256 remained in the blood significantly more than 153Gd-labeled saturated G6A-(1B4M)192 at later than 15 min postinjection (p &lt
0.01). In addition, G6E-(1B4M-Gd)256 visualized these finer vessels longer than G6A-(1B4M-Gd)192. The G6A-(1B4M-Gd)192 showed higher signal intensity in the kidney on the dynamic MR images and brighter kidney images than G6E-(1B4M-Gd)256. In conclusion, the G6A-(1B4M-Gd)192 was observed to go through glomerular filtration more efficiently than G6E-(1B4M-Gd)256 resulting faster clearance from the blood and higher renal accumulation, even though both of G6-1B4M conjugates have almost similar molecular size and same chemical structure. In terms of the ability of intravascular contrast agents, G6E-(1B4M-Gd)256 was better due to more Gd(III) atoms per molecule and longer retention in the circulation than G6A-(1B4M-Gd)192.