Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent

In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd3+, chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd3+ in GdDTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd3+ incubated with Ca2+ was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of.normal rats were observed by MR imaging. The content of free Gd3+, the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd3+ were released from Gd-DTPA-Pullulan after 2 h incubation with Ca2+ and Fe2+, respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t(1/2,alpha) = 0.43 h, t(1/2,beta) = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast (C) 2016 Elsevier B.V. All rights reserved.