Comparison of the macromolecular MR contrast agents with ethylenediamine-core versus ammonia-core generation-6 polyamidoamine dendrimer

Two novel macromolecular MRI contrast agents based upon generation-6 polyam idoamine dendrimers (G6) of presumed similar molecular size, but of differe nt molecular weight, were compared in terms of their blood retention, tissu e distribution, and renal excretion. Two G6s with either ammonia core (G6A) or with ethylenediamine core (G6E), which possessed 192 and 256 exterior p rimary amino groups, respectively, were used. These dendrimers were reacted with 2-(p-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid (1B4M). The G6-IB4M conjugates were reacted with Gd-153 for studying biodi stribution and blood clearance or Gd(III) for the MRI study. 3D-micro-MR an giography of the mice were taken with injection of 0.033 mmol of Gd/kg of G 6A-(1B4M-Gd)(192) or G6E-(1B4M-Gd)(256) using a 1.5-T superconductive MRI u nit. Although numerous fine vessels of similar to 100 mum diameter were vis ualized on subtracted 3D-MR-angiography with both G6A-(1B4M-Gd)(192) and G6 E-(1B4M-Gd)(256), Gd-153-labeled saturated G6E-(1B4M)(256) remained in the blood significantly more than Gd-153-labeled saturated G6A-(1B4M)(192) at l ater than 15 min postinjection (p < 0.01). In addition, G6E-(IB4M-Gd)(256) visualized these finer vessels longer than G6A-(1B4M-Gd)(192). The G6A-(1B4 M-Gd)(192) showed higher signal intensity in the kidney on the dynamic MR i mages and brighter kidney images than G6E-(1B4M-Gd)(256). In conclusion, th e G6A-(1B4M-Gd)(192) was observed to go through glomerular filtration more efficiently than G6E-(1B4M-Gd)(256) resulting faster clearance from the blo od and higher renal accumulation, even though both of G6-1B4M conjugates ha ve almost similar molecular size and same chemical structure. In terms of t he ability of intravascular contrast agents, G6E-(1B4M-Gd)(256) was better due to more Gd(III) atoms per molecule and longer retention in the circulat ion than G6A-(1B4M-Gd)(192).