Gadolinium-DTPA-dextran: A macromolecular MR blood pool contrast agent 1

Abstract

Magnetic resonance (MR) imaging blood pool agents offer numerous advantages for vascular and tumor imaging. The purpose of this study was to test gadolinium-diethylenetriaminepentaacetate-dextran ([Gd]DTPA-dextran) as a new water soluble macromolecular blood pool agent for MR imaging. [Gd]DTPA-dextran (187 gadolinium atoms per dextran, molecular weight 165 kD, diameter 17.6 nm) was synthesized. Fifteen anesthetized New Zealand White rabbits with thigh VX2 tumors were scanned in a knee coil at 1.5T. Coronal 3D MR angiographic sequences were obtained before and at several time points up to 72 hours after the intravenous bolus injection of [Gd]DTPA-dextran providing gadolinium at either 0.05 (n = 4) or 0.1 mmol/kg (n = 8) or [Gd]DTPA-bismethylamide (BMA) providing gadolinium at 0.1 mmol/kg (n = 3). Time enhancement curves for aorta, cava, and tumor rim were compared by univariate General Linear Model. Contrast enhancement of cava and aorta relative to a water phantom were significantly greater at all time points after either dose of [Gd]DTPA-dextran than after [Gd]DTPA-BMA (P < 0.01). Tumor rim enhancement was less intense for either dose of [Gd]DTPA-dextran at peak than for [Gd]DTPA-BMA (P < 0.05). Tumor rim enhancement with both doses of [Gd]DTPA-dextran became equivalent to that of [Gd]DTPA-BMA at one hour and was greater at 24 hours (P < 0.05). [Gd]DTPA-dextran is a new macromolecular MR contrast agent that can be synthesized to carry a high density of gadolinium atoms without intra-molecular cross-linking. It provides significantly greater vascular residence time than a conventional gadolinium chelate and shows promise for MR blood pool imaging.