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.

Graphical abstractAppending the pre-formed Gd(III) complex to the dendrimer or albumin is a far more convenient protocol and also significantly more advantageous not only for the characterization and relaxivity properties of albumin- or dendrimer-based agents, but with a potential impact to many macromolecular MR contrast agents.Figure optionsDownload full-size imageDownload as PowerPoint slide