High relaxivity magnetic resonance imaging contrast agents. Part 1. Impact of single donor atom substitution on relaxivity of serum albumin-bound gadolinium complexes.

Rationale And Objectives: The donor atoms that bind to gadolinium in contrast agents influence inner-sphere water exchange and electronic relaxation, both of which determine observed relaxivity. The effect of these molecular parameters on relaxivity is greatest when the contrast agent is protein bound. We sought to determine an optimal donor atom set to yield high relaxivity compounds.

High-relaxivity magnetic resonance imaging contrast agents. Part 2. Optimization of inner- and second-sphere relaxivity.

Rationale And Objectives: The observed relaxivity of gadolinium-based contrast agents has contributions from the water molecule(s) that bind directly to the gadolinium ion (inner-sphere water), long-lived water molecules and exchangeable protons that make up the second-sphere of coordination, and water molecules that diffuse near the contrast agent (outer-sphere). Inner- and second-sphere relaxivity can both be increased by optimization of the lifetimes of the water molecules and protons in these coordination spheres, the rotational motion of the complex, and the electronic relaxation of the gadolinium ion. We sought to identify new high-relaxivity contrast agents by systematically varying the donor atoms that bind directly to gadolinium to increase inner-sphere relaxivity and concurrently including substituents that influence the second-sphere relaxivity.

Synthesis and evaluation of a high relaxivity manganese(II)-based MRI contrast agent.

The manganese(II) ion has many favorable properties that lead to its potential use as an MRI contrast agent: high spin number, long electronic relaxation time, labile water exchange. The present work describes the design, synthesis, and evaluation of a novel Mn(II) complex (MnL1) based on EDTA and also contains a moiety that noncovalently binds the complex to serum albumin, the same moiety used in the gadolinium based contrast agent MS-325. Ultrafiltration albumin binding measurements (0.

The effect of a phosphodiester linking group on albumin binding, blood half-life, and relaxivity of intravascular diethylenetriaminepentaacetato aquo gadolinium(III) MRI contrast agents.

Amphiphilic gadolinium complexes were investigated as potential magnetic resonance imaging (MRI) contrast agents. A series of complexes was synthesized in order to study the effect of hydrophilic phosphodiester groups on albumin binding, relaxivity, and blood half-life in rats. Thus, compound 11a, a diethylenetriaminepentaacetato aquo gadolinium(III) (Gd-DTPA) derivative with an octyl substituent, was synthesized and compared to 5b, the analogous octyl derivative containing a phosphodiester linkage between the gadolinium chelate and the alkyl chain.