The uptake of Mn-DPDP by hepatocytes is not mediated by the facilitated transport of pyridoxine

Gallez, Bernard; Baudelet, Christine; Adline, Jacques; Charbon, V; Lambert, Didier M.

doi:10.1016/s0730-725x(96)00140-3

Cited by 14 publications

(8 citation statements)

References 24 publications

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“…Mn-DPDP is a manganese complex that does not enter into hepatocytes but releases divalent ions Mn 2ϩ inside hepatocytes. 9,10 In rats, hepatic SI enhancement after Mn-DPDP injection is reduced by a chronic (up to 5.5 months) ethanol diet 23 and in undifferentiated hepatocellular carcinoma. 24 In patients, cirrhosis also is associated with a low SI enhancement and the Child-Pugh index and the serum aspartate aminotransferase concentrations are related to the enhancement.…”

Section: Gd-bopta Entry Into Hepatocytes During Cirrhosismentioning

confidence: 99%

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Magnetic Resonance Imaging With Hepatospecific Contrast Agents in Cirrhotic Rat Livers

Planchamp¹,

Montet²,

Frossard³

et al. 2005

Investigative Radiology

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Objective: During biliary cirrhosis in rats, organic anion-transporting peptides (Oatps) and ATP-dependent multidrug resistance-associated protein 2 (Mrp2) that are likely to transport the contrast agent Gd-BOPTA through hepatocytes are down-regulated. However, the consequences of such down-regulation on the signal intensity (SI) enhancement are unknown. Consequently, the aim of our study was to measure the hepatic SI enhancement during Gd-BOPTA perfusion as well as the Oatp and Mrp2 expression in normal and cirrhotic livers. Materials and Methods:The hepatic SI enhancement during Gd-BOPTA perfusion was measured in livers isolated from normal rats and rats that had a bile duct ligation (BDL) 15, 30, and 60 days before the perfusion. Hepatic injury and transporter expression were measured in control and cirrhotic rats. Results: BDL induced a severe hepatic injury that increased over time with a down-regulation of the transporter expression. The extracellular space (assessed by Gd-DTPA perfusion) increased with the severity of the disease. Gd-BOPTA-induced SI enhancement remained similar in BDL-15 and BDL-30 rats than in control rats but significantly decreased in severe cirrhosis (BDL-60 rats). In comparison, the Mn-DPDP-induced SI enhancement decreases proportionally to the severity of the disease. Conclusion: During biliary cirrhosis, Gd-BOPTA-induced SI enhancement could not be related to the hepatic expression of transporters.

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Section: Gd-bopta Entry Into Hepatocytes During Cirrhosismentioning

confidence: 99%

“…In comparison, we measured the SI enhancement by MRI during the perfusion of Mn-DPDP, another hepato-specific MRI contrast agent that acts by releasing Mn 2ϩ into hepatocytes. 9,10 Consequently, Mn 2ϩ does not use membrane transporter of the Oatp family to enter into hepatocytes.…”

mentioning

confidence: 99%

Magnetic Resonance Imaging With Hepatospecific Contrast Agents in Cirrhotic Rat Livers

Planchamp¹,

Montet²,

Frossard³

et al. 2005

Investigative Radiology

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“…Mn-DPDP is a manganese chelate developed as an MR contrast agent for the hepatobiliary system. The DPDP complex is chemically related to pyridoxal phosphate, a vitamin B 6 analogue; therefore, uptake of Mn-DPDP into the hepatocytes via the vitamin B 6 pathway was expected [18]. Gd-EOB-DTPA is a paramagnetic hepatobiliary contrast agent with hepatocellular uptake via the anionic transporter protein [19,20].…”

Section: Discussionmentioning

confidence: 99%

Contrast-enhanced MR cholangiography: comparison of Gd-EOB-DTPA and Mn-DPDP in healthy volunteers

Bae

Na²,

Ds³

et al. 2012

BJR

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Objective: The purpose of this study was to compare the biliary enhancement dynamics of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid (Gd-EOB-DTPA) and mangafodipir trisodium (Mn-DPDP) for contrast-enhanced MR cholangiography (MRC) in healthy subjects. Methods: 15 healthy volunteers underwent MRI at 1.5 T with volumetric interpolated breath-hold examination sequence. Each volunteer was scanned once for each contrast agent. The signal-to-noise ratio (SNR) of the liver parenchyma and common hepatic duct (CHD) and the contrast-to-noise ratio (CNR) of CHD to liver parenchyma were evaluated and compared before and at several time points (5,15, 30, 45, 60, 90, and 120 min) after injection of each agent. Results: SNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP in liver parenchyma after 5 min and in CHD after 15 min (p,0.05). CNR of CHD to liver parenchyma using Gd-EOB-DTPA showed an initial decrease at 5 min post-injection followed by a steep increase to a peak at 15 min post-injection. CNR using Mn-DPDP showed a steady increase to a peak at 15 min post-injection without an initial decrease. At 15 min, the value of CNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP (p,0.05). Conclusion: For both contrast agents, CNR reached a peak at 15 min after contrast injection. At this time point, CNR of Gd-EOB-DTPA was significantly higher than that of Mn-DPDP. Therefore, Gd-EOB-DTPA may provide better contrast-enhanced MRC than Mn-DPDP at 15 min after contrast administration. The bile ducts are generally studied using fast spin echo T 2 weighted sequences with half-Fourier reconstruction. This conventional MR cholangiography (MRC) examination is highly accurate in detecting biliary tree disease [1,2]. However, the conventional MRC has diagnostic limitations, which include poor visualisation of the intrahepatic biliary tree compared with the extrahepatic biliary tree [3], limited spatial resolution and not being able to provide functional information of the biliary tree.Contrast-enhanced MRC has created interest in the field of MRC because of its potential to provide functional assessment and to improve the visualisation of the intrahepatic biliary trees [4][5][6]. The specific indications include pre-operative anatomical assessment of the biliary tree in preventing inadvertent complications in common laparoscopic cholecystectomy, and also in complex biliary surgical procedures such as biliary-enteric anastomosis and liver transplantation; post-operative assessment of the biliary tree after surgery when complications such as bile leak or inadvertent biliary tree stricture or ligation are suspected; and functional assessment of bile secretion and excretion [7][8][9].Contrast-enhanced MRC is performed with hepatobiliary MR contrast agents such as mangafodipir trisodium (Mn-DPDP), gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic-acid (Gd-EOB-DPTA) or gadobenate dimeglumine (Gd-BOPTA), which are administered intravenously, taken up by the hepatocytes, and then excreted via the biliary syste...

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“…Indeed, it was found that the Mn 2+ released by the complex was binding to proteins, this association being responsible for the large increase in the T 1 relaxivity . As a consequence of this set of evidence for the dissociation of the Mn complex, it was found that the transport into the hepatic cells was not mediated by the pyridoxine transporter . It also raised concerns about the possible accumulation of free manganese in the brain and possible associated toxicity .…”

Section: Characterization Of Mri Contrast Agents Properties With Eprmentioning

confidence: 99%

Electron paramagnetic resonance: a powerful tool to support magnetic resonance imaging research

Danhier

Gallez

2014

Contrast Media & Molecular

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The purpose of this paper is to describe some of the areas where electron paramagnetic resonance (EPR) has provided unique information to MRI developments. The field of application mainly encompasses the EPR characterization of MRI paramagnetic contrast agents (gadolinium and manganese chelates, nitroxides) and superparamagnetic agents (iron oxide particles). The combined use of MRI and EPR has also been used to qualify or disqualify sources of contrast in MRI. Illustrative examples are presented with attempts to qualify oxygen sensitive contrast (i.e. T1 - and T2 *-based methods), redox status or melanin content in tissues. Other areas are likely to benefit from the combined EPR/MRI approach, namely cell tracking studies. Finally, the combination of EPR and MRI studies on the same models provides invaluable data regarding tissue oxygenation, hemodynamics and energetics. Our description will be illustrative rather than exhaustive to give to the readers a flavour of 'what EPR can do for MRI'.

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The uptake of Mn-DPDP by hepatocytes is not mediated by the facilitated transport of pyridoxine

Cited by 14 publications

References 24 publications

Magnetic Resonance Imaging With Hepatospecific Contrast Agents in Cirrhotic Rat Livers

Magnetic Resonance Imaging With Hepatospecific Contrast Agents in Cirrhotic Rat Livers

Contrast-enhanced MR cholangiography: comparison of Gd-EOB-DTPA and Mn-DPDP in healthy volunteers

Electron paramagnetic resonance: a powerful tool to support magnetic resonance imaging research

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