Journal
CHEMICAL REVIEWS
Volume 119, Issue 2, Pages 957-1057Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrev.8b00363
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Funding
- German Research Foundation (DFG) [320225462]
- National Heart Lung and Blood Institute [K25HL128899, U54HL119145]
- National Institute for Biomedical Imaging and Bioengineering (NIBIB) [R21EB022804]
- NIBIB [R01EB009062, R21EB009738]
- National Cancer Institute [R01CA161221]
- National Institute for Diabetes and Digestive and Kidney Diseases [U01104302]
- National Instititute for Neurological Diseases and Stroke [R01NS091552]
- Pfizer
- Siemens
- Sanofi
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Tens of millions of contrast-enhanced magnetic resonance imaging (MRI) exams are performed annually around the world. The contrast agents, which improve diagnostic accuracy, are almost exclusively small, hydrophilic gadolinium(III) based chelates. In recent years concerns have arisen surrounding the long-term safety of these compounds, and this has spurred research into alternatives. There has also been a push to develop new molecularly targeted contrast agents or agents that can sense pathological changes in the local environment. This comprehensive review describes the state of the art of clinically approved contrast agents, their mechanism of action, and factors influencing their safety. From there we describe different mechanisms of generating MR image contrast such as relaxation, chemical exchange saturation transfer, and direct detection and the types of molecules that are effective for these purposes. Next we describe efforts to make safer contrast agents either by increasing relaxivity, increasing resistance to metal ion release, or by moving to gadolinium(III)-free alternatives. Finally we survey approaches to make contrast agents more specific for pathology either by direct biochemical targeting or by the design of responsive or activatable contrast agents.
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