Rebecca A. Wallace

Purification of X-ray contrast agent, magnetic resonance imaging agent, or radiopharmaceuticals using reverse osmosis

The use of reverse osmosis as an alternative or substitute method for the purification of a crude diagnostic agent. X-ray contrast agent, magnetic resonance imaging agent, or radiopharmaceuticals are purified by passing through a cross-linked reverse osmosis membrane.

Development of a novel nonaromatic small-molecule MR contrast agent for the blood pool

The ideal contrast agent for MR angiography should be safe, efficacious, blood-persistent, and easily excreted. The binding of small Gd chelates to macromolecules has been shown to provide a mechanism of proton relaxation enhancement in MR images through longer rotational correlation times of the macromolecule-bound Gd-chelate complexes (1,2). Several effective macromolecules bearing such covalently attached Gd chelates have been synthesized and evaluated previously for MRA applications. These, however, either proved unsafe (protein precipitants) or had undesirably long blood retention, ie, were not easily excreted (3-6). Reversible noncovalent binding of small Gd chelates to serum albumin (via hydrophobic interactions) produces an efficacious, blood persistent alternative to macromoleculebased MR blood-pool agents without attendant clearance problems (7,8). A prime requirement for this approach is the presence of a lipophilic component on the Gd chelate that can undergo reversible protein binding. An MR blood-pool agent, MS-325, which takes advantage of the binding of aromatic side chains on a Gd-chelate compound to albumin, is under development (2,7,8). We now report the results of our attempt to develop a nonaromatic small Gd 3+ chelate as a contrast agent for MR angiography (ie, MP-2269, a water-soluble MR agent that binds blood proteins reversibly to yield an efficacious blood-pool agent).