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Magnetic Resonance Imaging Contrast Agents

Magnetic Resonance Imaging Contrast Agents

Magnetic resonance imaging (MRI) is a radiation-free imaging modality with excellent contrast resolution and multiplanar capabilities. MRI has become one of the most important tools to screen humans in medicine. In MRI, image contrasts result from differences of water relaxation time and proton density between adjacent tissues. In many cases, however, there is no much difference between ordinary and diseased tissues, thus contrast agents are demanded to improve the sensitivity of MRI. By accelerating nuclear relaxation mainly via dipolar interactions, paramagnetic compounds can significantly enhance image contrast. As a paramagnetic substance, lanthanide complexes have attracted particular attention in the last decades. Gd3+ complexes were approved in the mid-eighties as MRI contrast agents and with over 30 million of injections per year, they represent the most widely applied lanthanide-drugs.


Paramagnetic coordination complex contrast agent achieves the contrast effect by altering the relaxation efficiency of water protons in the local tissues of the body to contrast with surrounding tissues. The efficiency with which a paramagnetic coordination complex contrast agent enhances the relaxation rate is termed relaxivity (ri) and is defined as the following equation [1]:

(1/Ti) = (1/Ti)0 + ri [CA]

In this equation, Ti refers to the relaxation time, (1/Ti) refers to the 1/Ti of the paramagnetic coordination complex contrast agent solution, (1/Ti)0 refers to the 1/Tof the paramagnetic coordination complex contrast agent-free solution, ri refers to the relaxivity, and [CA] is the millimolar concentration of the paramagnetic coordination complex contrast agent. Paramagnetic coordination complex contrast agents enhance both longitudinal (1/T1) and transverse (1/T2) relaxation rates. Gd3+-based contrast agents affect longitudinal and transverse relaxivities to a similar degree and are better suited for T1-weighted imaging.


Paramagnetic metal-based contrast agents shorten the relaxation time of protons due to dipole interactions between unpaired electrons and hydrogen nuclei, thus increasing the signal intensity. Although transition metal ions like Mn (II) and Fe (III) can also be used for MRI, the lanthanide gadolinium complexes are the most established contrast agent because the Gd (III) ion has seven unpaired electrons with a long electronic relaxation time leading to the largest effect compared to other paramagnetic ions. The anionic complexes Gd-DTPA (MAGNEVIST) and Gd-DOTA (DOTAREM) were the first complexes entered into clinical practice and they represent the reference compounds for the development and the evaluation of new agents. After a period of development, two neutral complexes, Gd-DTPA-BMA (OMNISCAN) and Gd-HP-DO3A (PROHANCE), have been introduced with the aim of providing systems with reduced osmotic potential for applications requiring higher doses of contrast agent. The specific parameters of the above four contrast agents are shown in table 1.

Table 1. Comparison of clinical data of Gd-based contrast agents

Contrast agent nameCommercial nameStructureMw/(g·mol-1)ri/(L·mmol-1·s-1)
Gd-DTPAMAGNEVISTLinear ionic5473.8
Gd-DOTADOTAREMMacrocyclic ionic5583.5
Gd-DTPA-BMAOMNISCANLinear nonionic5733.8
Gd-HP-DO3APROHANCEMacrocyclic nonionic5583.6

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