Inflammation targeted Gd3+-based MRI contrast agents imaging tumor and rheumatoid arthritis models

Arthur Ho Hon Leung, Jiefu Jin, Shuxia Wang, Hao Lei, Wing Tak Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

12 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1112-1123
Number of pages12
JournalBioconjugate Chemistry
Issue number6
Publication statusPublished - 18 Jun 2014

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology
  • General Medicine


Dive into the research topics of 'Inflammation targeted Gd3+-based MRI contrast agents imaging tumor and rheumatoid arthritis models'. Together they form a unique fingerprint.

Cite this