Method for Convection Enhanced Delivery of Therapeutic Agents

The invention is a method for monitoring the spatial distribution of therapeutic substances by MRI or CT that have been administered to tissue using convection-enhanced delivery, a technique that is the subject of NIH-owned U.S. Patent No. 5,720,720. In one embodiment, the tracer is a molecule, detectable by MRI or CT, which functions as a surrogate for the motion of the therapeutic agent through the solid tissue. In other particular embodiments, the tracer is the therapeutic agent conjugated to an imaging moiety. The method of this invention uses non-toxic macromolecular MRI contrast agents comprised of chelated Gd(III). In particular, the surrogate tracer used in this invention is a serum albumin conjugated with either a gadolinium chelate of 2-(p-isothiocyanotobenzyl)-6-methyldiethylenetriamine pentaacetic acid or with iopanoic acid. These macromolecular imaging agents have clearance properties that mimic the pharmacokinetic properties of co-administrated drugs, so as to be useful in quantifying the range and dosage level of therapeutic drugs using MR imaging.