Abstract

The authors developed and evaluated a polymer as a contrast agent for magnetic resonance (MR) angiography. The agent consists of a monomethoxy ether of poly(ethylene glycol) covalently attached to poly(L-lysine) (PL), with PL serving as the carrier of gadolinium diethylenetriaminepentaacetic acid (DTPA). Immunogenicity and toxicity studies were performed in mice, and biokinetic and metabolic studies were performed in rats. Dose response studies were performed with a three-dimensional time-of-flight sequence in eight rats. No permanent immune response was elicited against Gd-DTPA or the carrier molecule, and accumulation in organs of the reiculoendothelial system was minimal. The blood half-life of the agent was 14 hours. A dose of 20 mumol of gadolinium per kilogram of body weight was sufficient to increase the vessel-muscle ratio by four- to fivefold. Contrast was substantially improved and remained unchanged 2 hours after contrast medium administration, and good visualization of four orders of vasculature was allowed.