Initial clinical experience with oral manganese (CMC-001) for liver MR imaging

Abstract

Recently, a new oral liver-specific manganese-based MR agent (CMC-001) has been introduced. This contrast medium is delivered to the liver in high concentrations in the portal vein and very low doses in the hepatic artery, as only small amounts of manganese enter the general circulation. It is taken up by the hepatocytes and excreted in the bile. Our initial experience with the new MR contrast medium in a variety of patients is reported. A total of 20 patients (11 males and 9 females) were studied with MR imaging 2 h after oral ingestion of the contrast agent. Sixteen patients were referred for evaluation of focal liver lesion(s), whereas in the remaining four patients, evaluation of the biliary tract was requested. In the 17 patients without biliary obstruction, there was an increased signal intensity of the liver parenchyma, whereas in the three patients with biliary obstruction, the uptake was delayed. There was excellent visualization of the biliary system on the T1-weighted images in the 16 patients without biliary obstruction referred for evaluation of a focal liver lesion. In seven patients, the uptake was patchy. In patients with focal liver lesions or biliary tract diseases, it is possible to increase the signal intensity of the liver parenchyma after the oral intake of CMC-001. In patients without biliary tract obstruction, the biliary system is easily visualized. Oral manganese seems to be useful in hepatobiliary MRI. Further research is strongly warranted.

Manganese chloride tetrahydrate (CMC-001) enhanced liver MRI: evaluation of efficacy and safety in healthy volunteers

“…The observed AE after the administration of 1.6 g of CMC-001 were related to the high ion-content resulting in gastrointestinal discomfort, diarrhoea and nausea. Although not serious, AE after CMC-001 were numerous and clearly of higher frequency than those reported by others, being a factor that could potentially inhibit a widespread use (83)(84)(85)(86). Therefore we initiated the investigation presented in study IV, with the aim to investigate whether lowering the dose of MnCl 2 tetrahydrate could result in fewer AE but with a sufficient diagnostic imaging quality.…”

Oral manganese as an MRI contrast agent for the detection of nociceptive activity

“…Without knowing what minimum oral dose would be necessary to show the differential enhancement of peripheral nerves in this model of neuropathic pain, we chose to give a series of increasing oral doses. Manganese chloride has previously been given safely to human subjects at an oral dose of 1.6 g per ~70‐kg individual . We used this precedent as a starting point for our dosing, with an equivalent 1 × dose of 2.29 mg manganese chloride per 100 g body weight.…”

Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis

“…By adding for example vitamin D 3 and an amino acid, the uptake of manganese can be increased in the same way as with calcium (20). How much the uptake increases is not known, but THOMSEN et al demonstrated uptake in 12 consecutive volunteers (19) and 20 consecutive patients (18). Orally administered CMC-001 is excreted solely by bile; increased blood levels of manganese were not found (19), whereas 15% of intravenously administered manganese (mangafodipir trisodium) was eliminated by urine in 24 hours and 59% by feces in 5 days (2).…”

“…Oral administration offers some practical advantages, too, as it is not necessary to administrate it in the scanner room, or at the hospital. Further, it contains only nutritional ingredients, which reduce the risk of side effects (18).…”

“…However, it can be done immediately after lesion identification and, in that way, saves room time by diminishing the time between angiographic and parenchymal imaging. Like conventional extracellular gadolinium contrast agents, both Gd-BOPTA and Gd-EOB-DTPA can be used for arterial-venous phase imaging, but are limited by the fact that lesion detection from the hepatocyte uptake is performed after lesion characterization (18).…”