Inflammation targeted Gd(3+)-based MRI contrast agents imaging tumor and rheumatoid arthritis models
| Autor: | Shuxia Wang, Wing Tak Wong, Arthur Ho Hon Leung, Jiefu Jin, Hao Lei |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Mefenamic acid Biomedical Engineering Serum albumin Pharmaceutical Science Arthritis Contrast Media Mice Nude Bioengineering Inflammation Pharmacology Mycobacterium HeLa Arthritis Rheumatoid Mice In vivo Cell Line Tumor Neoplasms medicine Organometallic Compounds Animals Humans Rats Wistar Mice Inbred BALB C medicine.diagnostic_test biology Molecular Structure Chemistry Organic Chemistry Magnetic resonance imaging medicine.disease biology.organism_classification Magnetic Resonance Imaging Rats Disease Models Animal Rheumatoid arthritis biology.protein medicine.symptom Biotechnology medicine.drug HeLa Cells |
| Zdroj: | Bioconjugate chemistry. 25(6) |
| ISSN: | 1520-4812 |
| Popis: | 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 Gd(3+) 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. |
| Databáze: | OpenAIRE |
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