Journal
MEDCHEMCOMM
Volume 3, Issue 5, Pages 552-565Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2md00279e
Keywords
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Funding
- Biomedical Research Council
- COT [ETPL/10-S10COT-006]
- A*STAR (Agency for Science, Technology and Research), Singapore [1131CFG002]
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Paramagnetic Gd(III) chelate contrast agents have been extensively used to enhance the signal of MRI scans for the last three decades. The use of Gd(III) chelate contrast agents is projected to increase as new agents and applications arise, thanks to the favorable combination of a large magnetic moment and long electron spin relaxation time of the Gd(III) ion. The relaxivity and stability of Gd(III) chelates are the primary requisites for the development of contrast agents as both small doses and low release of free Gd(III) ions will reduce the toxicity. The physico-chemical parameters and structure-related relaxation mechanisms provide the strategies for chelate design. The higher relaxivity and efficacy of the contrast agent can be improved by designing pH-, metal ion-, enzyme- or small biomolecule-dependent smart contrast agents. Through conjugation to biomacromolecules such as polymers, dendrimers or non-covalent binding to plasma proteins, contrast agents could increase the blood half-life and can be used for contrast-enhanced MRI. When conjugated to certain diagnostic or therapeutic proteins, low molecular weight Gd(m) chelates could cross the blood-brain barrier (BBB) by means of a receptor-mediated transport system or receptor-mediated transcytosis.
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