Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/13425
Title: Inflammation targeted Gd3+-based MRI contrast agents imaging tumor and rheumatoid arthritis models
Authors: Leung, AHH
Jin, J
Wang, S
Lei, H
Wong, WT 
Issue Date: 2014
Publisher: American Chemical Society
Source: Bioconjugate chemistry, 2014, v. 25, no. 6, p. 1112-1123 How to cite?
Journal: Bioconjugate Chemistry 
Abstract: Inflammatory responses are closely related to cancer progression and several diseases. Anti-inflammatory drugs that bind to inducible enzymes can be used as biomarkers for molecular imaging. Selective targeted contrast agents are expected to improve contrast-to-noise ratio (CNR) in MRI at the site of inflammation. In this work, three new Gd3+ DO3A-amide MRI contrast agents (CAs) that conjugated to mefenamic acid (MA), a commonly used nonsteroidal anti-inflammatory drug (NSAID), through different linkers, ethylenediamine (GdL1), 2,2′-oxidiethylamine (GdL2) and 4,7,10-trioxa-1,13-tridecanediamine (GdL3) were studied. Their relaxivities were GdL1 (4.74 mM-1 s-1), GdL2 (4.77 mM-1 s -1), and GdL3 (4.95 mM-1 s-1) at 400 MHz at 25 °C. Their serum albumin binding properties were studied by tryptophan emission-quenching experiments, with GdL1 showing a preferential binding toward HSA and BSA as compared with GdL2 and GdL3. They showed low cytotoxicities toward HeLa cells at high concentration (0.5 mM) and high cellular uptake in U87 cells as compared with GdDOTA. In vivo MRI showed increased T1-weighted contrast after intravenous injection of the agents. Moreover, T1 contrast was significantly enhanced for 1.5 h in the U87 tumor model and 2 h in the arthritis joint in adjuvant-induced arthritis (AIA) model at dosages of 0.1 and 0.03 mmol/kg, respectively. Most of the agents were cleared at 24 h post-administration in the AIA model with no observable T1 contrast. GdL1-3 showed superior retentions and intensity enhancements (IEs) at the kidney, liver, tumor, and arthritis joint to those of GdDOTA. GdL3 showed the highest relaxivity and IE at the arthritis joint and is therefore a potential candidate to be developed as MRI CAs that target inflammation.
URI: http://hdl.handle.net/10397/13425
ISSN: 1043-1802
DOI: 10.1021/bc5001356
Appears in Collections:Journal/Magazine Article

Access
View full-text via PolyU eLinks SFX Query
Show full item record

SCOPUSTM   
Citations

3
Last Week
0
Last month
0
Citations as of Aug 13, 2017

WEB OF SCIENCETM
Citations

3
Last Week
0
Last month
0
Citations as of Aug 14, 2017

Page view(s)

36
Last Week
4
Last month
Checked on Aug 13, 2017

Google ScholarTM

Check

Altmetric



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.