Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications

Abstract

Hepatobiliary contrast agents with uptake into hepatocytes followed by variable biliary excretion represent a unique class of cell-specific MR contrast agents. Two hepatobiliary contrast agents, mangafodipir trisodium and gadobenate dimeglumine, are already clinically approved. A third hepatobiliary contrast agent, Gd-EOB-DTPA, is under consideration. The purpose of this review is to provide an overview on the properties, clinical development and application of these three hepatobiliary contrast agents. Bolus injectable paramagnetic hepatobiliary contrast agents combine established features of extracellular agents with the advantages of hepatocyte specificity. The detection and characterisation of focal liver disease appears to be improved compared to unenhanced MRI, MRI with unspecific contrast agents and contrast-enhanced CT. To decrease the total time spent by a patient in the MR scanner, it is advisable to administer the agent immediately after acquisition of unenhanced T1-w MRI. After infusion or bolus injection (with dynamic FS-T1-w 2D or 3D GRE) of the contrast agent, moderately and heavily T2w images are acquired. Post-contrast T1-w MRI is started upon completion of T2-w MRI for mangafodipir trisodium and Gd-EOB-DTPA as early as 20 min following injection, while gadobenate dimeglumine scans are obtained >60 min following injection. Post-contrast acquisition techniques with near isotropic 3D pulse sequences with fat saturation parallel the technical progress made by MSCT combined with an unparalleled improvement in tumour-liver contrast. The individual decision that hepatobiliary contrast agent one uses is partly based on personal preferences. No comparative studies have been conducted comparing the advantages or disadvantages of all three agents directly against each other.

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“…the dextran coat is degraded and eliminated via the kidneys, whereas the iron oxides are distributed to the normal iron metabolism, such as heme synthesis or storage in the liver (29,31). Of note, ferucarbotran showed an excellent safety profile in phase I-III studies (31,32).…”

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“…Its magnetic properties in T 2 are characterised by high relaxivity: r 2 = 190 l/mmol/second (Table S1). 18,25,26 Biodistribution studies in humans and rats have shown that 80% of the intravenous dose is captured by the liver. 18,25 Ferucarbotran can also be used with T 1 -weighted sequences, like gadolinium chelates, during its initial intravascular distribution phase.…”

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