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Object: To evaluate the efficacy of three dose levels of the oral hepatobiliary manganese-based magnetic resonance imaging (MRI) contrast agent CMC-001, and assess its safety profile and patient acceptability., Materials and Methods: After ethics committee approval, 32 healthy volunteers (males/females: 18/14) were included. Liver MRI was performed before and 3 h after ingestion of 0.8, 0.4, and 0.2 g of CMC-001 on separate occasions. Liver-to-muscle signal intensity (SI) ratio from baseline to post-contrast and image quality was assessed. Adverse drug reactions/adverse events (ADRs/AEs) and clinico-laboratory tests were monitored., Results: The increase in liver-to-muscle SI ratio was significantly higher after 0.8 g (0.696) compared to 0.4 g (0.458) and 0.2 g (0.223) (in all pair-wise comparisons, P < 0.0001). The overall image quality was superior after 0.8 g. ADRs/AEs were dose-related and predominantly of mild intensity., Conclusion: Liver MRI using 0.8 g CMC-001 has the highest efficacy and still acceptable ADRs and should therefore be preferred.

Manganese is one of the most abundant metals on earth and is found as a component of more than 100 different minerals. Besides being an essential trace element in relation to the metabolic processes in the body, manganese is also a paramagnetic metal that possesses similar characteristics to gadolinium with regards to T1-weighted (T1-w) magnetic resonance imaging (MRI). Manganese, in the form of manganese (II) chloride tetrahydrate, is the active substance in a new targeted oral contrast agent, currently known as CMC-001, indicated for hepatobiliary MRI. Under physiological circumstances manganese is poorly absorbed from the intestine after oral intake, but by the use of specific absorption promoters, L-alanine and vitamin D(3), it is possible to obtain a sufficiently high concentration in the liver in order to achieve a significant signal enhancing effect. In the liver manganese is exposed to a very high first-pass effect, up to 98%, which prevents the metal from reaching the systemic circulation, thereby reducing the number of systemic side-effects. Manganese is one of the least toxic trace elements, and due to its favorable safety profile it may be an attractive alternative to gadolinium-based contrast agents for patients undergoing an MRI evaluation for liver metastases in the future. In this review the basic pharmacological and pharmaceutical aspects of this new targeted oral hepatobiliary specific contrast agent will be discussed.

Objectives: To compare the sensitivity of MRI to detect colorectal cancer liver metastases (CRLM) after ingestion of manganese-based contrast agent (CMC-001) with that of a comprehensive intravenous gadobenate dimeglumine protocol, and to assess the safety and acceptability of oral manganese., Methods: 20 patients suspected of having 1-6 CRLM were included prospectively in this randomised cross-over study. Liver MRI was performed with a one-week interval at 1.5 T and included T1-w VIBE and T2-HASTE, before and after administration of 1.6 g CMC-001 or 0.1 mmol/kg gadobenate dimeglumine. The metastasis-to-liver signal intensity (SI) ratio was calculated. Standard of reference was histopathology after surgery, or combination of other imaging studies and/or follow up. Adverse events (AE) and clinicolaboratory tests were monitored., Results: Of 44 metastases, 41 were detected after CMC-001 (93%) and 42 after gadobenate dimeglumine (95%). Fifteen false-positive lesions were found after CMC-001 and 2 after gadobenate dimeglumine. The metastasis-to-liver SI ratio was significantly higher after CMC-001 than after gadobenate dimeglumine (0.51 and 0.21 respectively, P < 0.0001). More AE occurred after manganese compared to gadobenate dimeglumine., Conclusions: CMC-001 is as sensitive as an extensive intravenous gadobenate dimeglumine protocol in detecting CRLM. It was relatively well tolerated but had higher rates of gastrointestinal AE., Key Points: • Liver MRI after ingestion of manganese is highly sensitive for detecting metastases • High false-positive rate necessitates further evaluation, in some cases • The MR examination time is short • Oral ingestion of manganese seems safe and relatively well tolerated by patients • Manganese compounds may be useful for liver metastasis surveillance after colorectal cancer.