Effect of varying the molecular weight of the MR contrast agent Gd-DTPA-polylysine on blood pharmacokinetics and enhancement patterns

Abstract

The effects of varying the molecular weight of gadolinium-DTPA (diethylenetriaminepentaacetic acid)-polylysine, a macromolecular magnetic resonance (MR) imaging contrast agent, on blood pharmacokinetics and dynamic tissue MR imaging signal enhancement characteristics were studied in normal rats. Blood elimination half-life, total blood clearance, volume of the central compartment (Vcc) and the steady-state distribution volume (Vssd) were calculated for four Gd-DTPA-polylysine polymers with average molecular weights of 36, 43.9, 139, and 480 kd and compared with corresponding values for Gd-DTPA (0.57 kd) and Gd-DTPA-albumin (92 kd). Blood elimination half-life increased seven-fold with an increase in molecular weight from 36 to 480 kd. The Vcc values for all polylysine polymers did not differ significantly from the Vcc value for Gd-DTPA-albumin but were significantly smaller than the Vcc value for Gd-DTPA. The Vssd value for Gd-DTPA did not differ significantly from the Vssd value for the 36- and 43.9-kd polymers but was significantly larger than the Vssd values for the 139- and 480-kd polymers and for Gd-DTPA-albumin. On T1-weighted coronal spin-echo MR images, dynamic signal enhancement profiles in liver and kidney for the 36-, 43.9-, and 480-kd Gd-DTPA-polylysine chelates corresponded to the blood pharmacokinetic data. Increasing molecular weight of Gd-DTPA-polylysine formulations substantially slows blood clearance and produces a prolonged, almost constant tissue signal enhancement for the 60-minute observation period.