Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI.

We report in vivo and in vitro MRI properties of six gadolinium-dendrimer and gadolinium-albumin conjugates of derivatized acyclic diethylenetriamine-N,N',N',N″, N″-pentaacetic acid (1B4M) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (C-DOTA). The three albumin-based agents have comparable protein to chelate ratios (1:16-18) as well as molar relaxivity (8.8-10.4 mM(-1) s(-1)). The three dendrimer based agents have blood clearance half-lives ranging from 17 to 66 min while that of the three albumin-based agents are comparable to one another (40-47 min). The dynamic image obtained from use of the albumin conjugate based on the macrocycle (C-DOTA) showed a higher contrast compared to the remaining two albumin based agents. Our conclusion from all of the results is that the macrocyclic-based (DOTA) agents are more suitable than the acyclic-based (1B4M) agent for in vivo use based on their MRI properties combined with the kinetic inertness property associated with the more stable Gd(III) DOTA complex.