Journal
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 61, Issue -, Pages 659-664Publisher
ELSEVIER
DOI: 10.1016/j.msec.2016.01.008
Keywords
Gadolinium-DTPA; Nephrogenic fibrosis; Extended blood circulation; Transmetalation; Chelation stability
Categories
Funding
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2014K2A2A2000720, 2014R1A2A2A04006562]
- National Research Foundation of Korea [2014R1A2A2A04006562, 21A20132112043] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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