Mn‐DPDP–enhanced MR imaging of malignant liver lesions: Efficacy and safety in 20 patients

Abstract

Twenty patients with malignant liver lesions underwent magnetic resonance (MR) imaging with manganese (II) DPDP [N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate)] to evaluate the safety and efficacy of the contrast agent. In two groups of 10 patients each, 5 mumol/kg Mn-DPDP was administered intravenously (3 mL/min) at a concentration of either 50 or 10 mumol/mL. T1- and T2-weighted images were obtained with a 1.5-T imager. Six patients reported a total of eight instances of side effects (flush, feeling of warmth, metallic taste) of which seven occurred at the 50 mumol/mL concentration. A significant decrease in alkaline phosphatase levels 2 hours after injection was recorded. On T1-weighted images, the 10 mumol/mL formulation yielded significantly greater increases in contrast-to-noise ratio (79.8%-137.5%) than the 50 mumol/mL formulation (46.2%-86.6%). In a blinded reader study of 10 patients with one to five lesions each, no lesion was missed on Mn-DPDP--enhanced T1-weighted images; however, four false-positive foci were identified. The authors conclude that slow administration of 5 mumol/kg Mn-DPDP at a concentration of 10 mumol/mL is safe and efficient enough to proceed to further clinical trials.

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

“…A dosage of 10 µmol kg −1 was superior to 5 µmol kg −1 in terms of tumour-liver contrast, without increasing the rate of adverse events [20]. However, mangafodipir trisodium at 5 µmol kg −1 improved liver tumour contrast by 46.2-79.8% on T1w SE and by 86.6-137.5% on T1w GRE images in a phase-2 study [38]. The findings were supported by the study of Schima et al in which tumour-liver contrast was even more increased on mangafodipir-enhanced images (131% on T1w SE and 218% on T1w GRE images) [7].…”

“…As already mentioned, the enhancement effect is more pronounced on T1w GRE than on T1w SE images [7,38]. In general, T1w GRE pulse sequences optimised for liver tumour contrast on unenhanced T1w images are also suitable for mangafodipir-enhanced MR imaging of the liver and pancreas [17].…”

Safety of MR liver specific contrast media

“…Flushing and warmth were reported in 21/141 patients (14%), and nausea in three (2.1%). In 1993, Aicher et al [25] reported side effects in 6/20 (30%) patients, including flushing, warmth and/or metallic taste. The results of a small European phase III trial that included 82 patients reported mild or moderate adverse events in 17% while 4% experienced infusion related discomfort [26].…”

Orally Administered Manganese With and Without Ascorbic Acid as a Liver-Specific Contrast Agent and Bowel Marker for Magnetic Resonance Imaging

“…10,11 Even if these side-effects in clinical use with mangafodipir using administrations at the dose 5 moL/kg causes little effect on blood pressure, pulse rate, and electrocardiography, there may be side effects as facial flushing, sensations of warmth, and nausea. 12 Oral administration instead of intravenous, has early been suggested for administration of a Mn-containing contrast medium for liver imaging, [13][14][15] but has not until recently been pursued clinically. There are several potential advantages of oral administration of a liver-specific CM as (i) higher patient tolerance and comfort compared with intravenous injection, (ii) a combination of the liver enhancement and delineation of the gastrointestinal tract, and (iii) reduction of systemic side effects.…”