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

Materials Science & Engineering. C, Materials for Biological Applications
Ratchapol JenjobSu-Geun Yang

Abstract

In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd(3+), chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd(3+) in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd(3+) incubated with Ca(2+) 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 Gd(3+), 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 Gd(3+) were released from Gd-DTPA-Pullulan after 2h incubation with Ca(2+) and Fe(2+), respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t1/2,α=0.43 h, t1/2,β=2.32 h), much longer than 0.11h 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-lif...Continue Reading

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Citations

Apr 25, 2019·Macromolecular Bioscience·Ratchapol JenjobDaniel Crespy
May 1, 2020·Biomaterials Science·Ratchapol JenjobDaniel Crespy
Aug 20, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Siyu ChenQuan Zhou
Jul 27, 2021·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Hoa Phuong TranSu-Geun Yang

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