Polymeric Gadolinium Chelate Magnetic Resonance Imaging Contrast Agents:  Design, Synthesis, and Properties

Abstract

We have synthesized and evaluated five series of polymeric gadolinium chelates which are of interest as potential MRI blood pool contrast agents. The polymers were designed so that important physical properties including molecular weight, relaxivity, metal content, viscosity, and chelate stability could be varied. We have shown that, by selecting polymers of the appropriate MW, extended blood pool retention can be achieved. In addition, relaxivity can be manipulated by changing the polymer rigidity, metal content affected by monomer selection, viscosity by polymer shape, and chelate stability by chelator selection.

Pharmacokinetics and Tissue Retention of (Gd-DTPA)-Cystamine Copolymers, a Biodegradable Macromolecular Magnetic Resonance Imaging Contrast Agent

“…Macromolecular Gd(III) complexes have a potential for improved blood pool pharmacokinetics and MR contrast enhancement when compared to low-molecular-weight Gd(III) complexes (4)(5)(6). A number of macromolecular Gd(III) complexes have been prepared as blood pool MRI contrast agents (7)(8)(9)(10)(11)(12)(13). Macromolecular Gd(III) complexes significantly increase blood pool and tissue retention time of contrast agents, resulting in superior contrast enhancement in animal models.…”

Gd-DTPA l-Cystine Bisamide Copolymers as Novel Biodegradable Macromolecular Contrast Agents for MR Blood Pool Imaging

“…However, their clinical application is limited because of their transient tissue retention and unfavorable pharmacokinetics, which includes rapid extravasation from the cardiovasculature and undiscriminable distribution into the extracellular space (5,6). As a result, macromolecular Gd(III) chelates have been developed as blood pool MRI contrast agents to modify in vivo pharmacokinetics (5Y9).…”

MRI with Gadolinium‐Based Nanoparticles

“…The best results were obtained with a dOTA dendrimer that was the result of the incorporation of optimized features, that is, high rigidity, low viscosity, high number of Gd 3+ chelate, and high stability provided by the dOTA. These combined characteristics contributed to a long blood half-life and a high relaxivity [55]. …”