Evidence for the dissociation of the hepatobiliary MRI contrast agent Mn‐DPDP

Gallez, Bernard; Bačić, Goran; Swartz, Harold M.

doi:10.1002/mrm.1910350104

Cited by 88 publications

(63 citation statements)

References 39 publications

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“…35 Furthermore, MnDPDP has been successfully utilized for imaging cardiac ischemia. 34,[36][37][38] It is interesting to note that much of the Mn 2þ in MnDPDP comes off the chelate slowly after administration, 39 which implies some of the tissue enhancement detected with MnDPDP was due to Mn 2þ .…”

Section: Manganese Is An Intracellular Contrast Agentmentioning

confidence: 99%

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

et al. 2004

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Manganese-enhanced MRI (MEMRI) is being increasingly used for MRI in animals due to the unique T 1 contrast that is sensitive to a number of biological processes. Three specific uses of MEMRI have been demonstrated: to visualize activity in the brain and the heart; to trace neuronal specific connections in the brain; and to enhance the brain cytoarchitecture after a systemic dose. Based on an ever-growing number of applications, MEMRI is proving useful as a new molecular imaging method to visualize functional neural circuits and anatomy as well as function in the brain in vivo. Paramount to the successful application of MEMRI is the ability to deliver Mn 2þ to the site of interest at an appropriate dose and in a time-efficient manner. A major drawback to the use of Mn 2þ as a contrast agent is its cellular toxicity. Therefore, it is critical to use as low a dose as possible. In the present work the different approaches to MEMRI are reviewed from a practical standpoint. Emphasis is given to the experimental methodology of how to achieve significant, yet safe, amounts of Mn 2þ to the target areas of interest.

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Section: Manganese Is An Intracellular Contrast Agentmentioning

confidence: 99%

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

et al. 2004

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“…We anticipate that the full exploitation of this capability, however, will require the widespread availability of in vivo EPR in the clinical setting. In the meantime, of course, this technique is already being applied increasingly widely in vivo in experimental pharmacology for uses including: tracers of the distribution, metabolism, and excretion of paramagnetically tagged drugs 28,91 following the state of systems such as liposomes; 92 monitoring the distribution and status of NMR contrast agents; 21,[93][94][95][96] determining the occurrence of free radical intermediates of drugs and potential toxins; 97,98 determining the effects of anesthetics on pO 2 in the brain; [99][100][101] following the stability of spin traps and their adducts in vivo, 5,102 following the distribution and valence state of chromium in vivo, [103][104][105] and following the effect of drugs on the pH in the stomach. 106 …”

Section: Strategy For the Long-term Development Of Clinical Applicatimentioning

confidence: 99%

Clinical applications of EPR: overview and perspectives

et al. 2004

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The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repeated and accurate measurements of pO 2 in tissues. Such measurements can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology, peripheral vascular disease and wound healing. The other area of immediate and timely importance is the unique ability of in vivo EPR to measure clinically significant exposures to ionizing radiation 'after-the-fact', such as may occur due to accidents, terrorism or nuclear war. There are a number of other capabilities of in vivo EPR that also potentially could become extensively used in human subjects. In pharmacology the unique capabilities of in vivo EPR to detect and characterize free radicals could be applied to measure free radical intermediates from drugs and oxidative process. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. These often unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, molecular motion, charge) have already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for extending clinical uses of in vivo EPR. The challenges for achieving full implementation include adapting the spectrometer for safe and comfortable measurements in human subjects, achieving sufficient sensitivity for measurements at the sites of the pathophysiological processes that are being measured, and establishing a consensus on the clinical value of the measurements.

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“…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.…”

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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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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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Evidence for the dissociation of the hepatobiliary MRI contrast agent Mn‐DPDP

Cited by 88 publications

References 39 publications

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

Clinical applications of EPR: overview and perspectives

Magnetic Resonance Imaging With Hepatospecific Contrast Agents in Cirrhotic Rat Livers

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