Hepatobiliary/GI Application Tips: Mangafodipir Trisodium (Mn-DPDP)

Mangafodipir trisodium [Mn-DPDP (Manganese Dipyridoxal Diphosphate), Teslascan] is a chelate of paramagnetic manganese that is used as a hepatocyte specific MRI contrast agent . It is indicated for intravenous administration as an adjunct to MRI in patients to enhance the T1-weighted images used in the detection, localization, characterization, and evaluation of lesions of the liver. The Mn-DPDP chelate dissociates rapidly in the blood following intravenous infusion to release free Mn ++ ion. The free Mn ++ ion is then taken up and metabolized by parenchymal cells, particularly those of the liver, pancreas, kidneys, and adrenals and excreted primarily (> 50%) via the biliary system . Liver uptake of manganese is rapid, with peak enhancement occurring within 10-20 minutes and lasts for approximately 4 hours. Imaging can begin within minutes of injection, and additional scans can be taken up to 24 hours later without re-injection or loss of image quality. Teslascan is reasonably well tolerated with reported minor reactions including facial flushing, nausea, vomiting, and transient increase in blood pressure. It should be used with caution in patients with cholestasis, unless extrahepatic cholestasis is corrected by biliary drainage.

Teslascan shortens the T1 relaxation time thereby increasing the signal intensity of normal liver on T1-weighted images, an effect that is best seen on fat-saturation techniques. T2-weighted images are not affected by Mn-DPDP; therefore, this contrast agent is often injected immediately after pre-contrast T1-weighted images. Because of the selective increase in the T1 signal intensity of the liver on T1-weighted images, Teslascan increases lesion-to-liver contrast. Tumors of non-hepatocellular origin, e.g. colorectal metastases, do not demonstrate uptake of the Teslascan contrast resulting in increased lesion conspicuity. Several studies have shown improved lesion detection on images obtain after Teslascan infusion when compared with pre-contrast images. However, hepatocellular lesions derived from well-differentiated hepatocytes, such as hepatocellular carcinoma (HCC), hepatocellular adenomas, and FNH, will also take up the Teslascan contrast resulting in enhancement of these lesions and, therefore, these lesions will be obscured on post-contrast images. Because of this phenomena, a study aimed at evaluating Teslascan for the evaluation of hepatocellular tumors demonstrated poor efficacy of this agent to hepatocellular based lesions. However, the uptake itself allowed for identification of additional lesions not seen on unenhanced imaging, but at the expense of converting other lesions clearly identified to isointense lesions. Moreover, Teslascan accumulation has also been observed in hepatic metastases from nonfunctioning endocrine tumors of the pancreas. In a recent study in 77 patients with histologically confirmed lesions, Mn-DPDP enhanced MRI had a sensitivity and specificity of 91% and 67%, respectively, for the differentiation of malignant versus benign liver lesions, and 91% and 85%, respectively, for the differentiation of hepatocellular versus non-hepatocellular lesions. In addition to improved lesion detection, Teslascan facilitates lesion localization by the high vessel-to-liver contrast. The use of Teslascan in the cirrhotic liver for the detection of HCC is limited due to the heterogeneous uptake of the contrast agent secondary to areas of hepatic fibrosis. Lastly, because Teslascan is excreted primarily by the biliary system, Teslascan T1-weighted MR imaging may serve as a supplement to conventional MR cholangiograhic methods to facilitate the definition of intrahepatic bile duct anatomy in non-obstructed biliary systems, such as those seen in healthy liver transplant donor candidates.

Teslascan is an isotonic, clear, yellow solution that is available as a ready-to-use formulation at a concentration of 0.01 mmol/ml in 50ml glass vials. The clinical dose is 5 µmol/kg body weight, which equals 0.5 ml/kg body weight. The mode of administration is intravenous infusion at a slow rate of 2-3 ml/min.

Prior to the administration of any contrast material, breath-hold axial and coronal half-Fourier acquisition single-shot turbo spin echo (HASTE) images are acquired using the following parameters: TR/effective TE/refocusing angle = ¥ /62 ms/140-160 ° , imaging matrix of 128-192 x 256, field of view 300 - 375 mm, 4 mm slice thickness, rectangular field of view depending on body habitus, 15 – 20 slices per breath hold . At least three oblique coronal heavily T2-weighted turbo spin echo imaging (TR/effective TE/flip angle, 2800/1100/150-180 ° , matrix 240 x 256, field of view 300-375 mm, 20-60 mm section thickness with optional rectangular field-of-view) is also performed, each within a single breath hold acquisition.

At the end of the routine MRCP exam, an intravenous injection of Teslascan at a standard dose of 5 m mol/kg (0.1 ml/kg, up to a maximum of 15 ml) is administered via a slow injection over 1 to 2 minutes followed by a 10 ml saline flush. Ten to 15 minutes after injection, axial and coronal volumetric 3D spoiled gradient echo acquisitions of the liver and biliary system is performed using two volumetric interpolated breath-hold exam sequences with intermittent fat-suppression pulses: a higher resolution sequence acquired coronally with limited coverage through the biliary ducts: TR/TE/flip angle = 6.8/2.3/25-40 ° , 128-256 x 512 matrix, 350-450 mm FOV using rectangular field-of-view depending on body habitus, 24 partitions interpolated to 48 slices with £ 1.5 mm thickness; and, a lower resolution sequence performed axially to include the entire liver: TR/TE/flip angle = 4.5/1.9/25-40 ° , 128-160 x 256 matrix, 300-375 mm FOV using rectangular field-of-view, and 80-112 partitions for £ 2 mm slice thickness (18) . Imaging time for all sequences is kept less than 25 seconds to facilitate breath-holding during the acquisition. Subsequent post-processing such as subtraction and multiplanar reconstructions can be performed on the post-Teslascan sequence for better delineation of hepatobiliary anatomy.