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

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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 sevenfold 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 pharma‐cokinetic 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.