Tissue-specific MR contrast agents

doi:10.1016/S0720-048X(02)00332-7

European Journal of Radiology

Volume 46, Issue 1, April 2003, Pages 33-44

https://doi.org/10.1016/S0720-048X(02)00332-7 Get rights and content

Abstract

The purpose of this review is to outline recent trends in contrast agent development for magnetic resonance imaging. Up to now, small molecular weight gadolinium chelates are the workhorse in contrast enhanced MRI. These first generation MR contrast agents distribute into the intravascular and interstitial space, thus allowing the evaluation of physiological parameters, such as the status or existence of the blood–brain-barrier or the renal function. Shortly after the first clinical use of paramagnetic metallochelates in 1983, compounds were suggested for liver imaging and enhancing a cardiac infarct. Meanwhile, liver specific contrast agents based on gadolinium, manganese or iron become reality. Dedicated blood pool agents will be available within the next years. These gadolinium or iron agents will be beneficial for longer lasting MRA procedures, such as cardiac imaging. Contrast enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Metastatic involvement will be seen either after the injection of ultrasmall superparamagnetic iron oxides or dedicated gadolinium chelates. The accumulation of both compound classes is triggered by an uptake into macrophages. It is likely that similar agents will augment MRI of atheriosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on small gadolinium labeled peptides are on the horizon. It is very obvious that the future of cardiovascular MRI will benefit from the development of new paramagnetic and superparamagnetic substances. The expectations for new tumor-, pathology- or receptor-specific agents are high. However, is not likely that such a compound will be available for daily routine MRI within the next decade.

Introduction

The clinical introduction of magnetic resonance imaging (MRI) in the early 1980s revolutionized diagnostic imaging. The breath-taking progress in computer technology has made multidimensional imaging a reality, producing images within seconds without time-consuming data processing. These techniques allow physicians to accurately diagnose many pathologies noninvasively. The use of paramagnetic metallochelates makes the method even more sensitive and the diagnosis more specific.

The first generation MR contrast agents distribute into the intravascular and interstitial space. These often called ‘unspecific agents’ allow the evaluation of physiological parameters, such as the status or existence of the blood–brain-barrier or the renal function. However, compounds with a tissue-specific distribution to detect focal anomalies or evaluate tissue function may be desirable to improve diagnostic accuracy. The definition of ‘tissue-specific distribution’ is not a simple matter, since an extracellular agent also distributes specifically in the body. Agents such as Magnevist® elicit an extraordinary organ-specific distribution due to their glomerular filtration. These renal-specific agents accumulate in the kidneys at much higher concentrations than in the blood or any other tissue. Another recently found, remarkable feature of so-called unspecific compounds is their ability to discriminate between viable and nonviable myocardium [1]. Extracellular agents can elicit properties of necrosis-specific compounds [2], [3], [4]. In many cases, analysis of enhancement kinetics allows a classification of the pathology; for example, a fast increase in signal intensity is more characteristic of a mamma carcinoma than a benign process [5], [6]. A pharmacokinetic interpretation of enhancement kinetics is helpful in assessing physiological parameters, such as tumor angiogenesis and microvessel density [7]. Analysis of the bolus kinetics of these unspecific agents can also determine cerebral blood flow and volume [8].

Shortly after the first clinical use of paramagnetic metallochelates, the first attempts at targeting paramagnetic substances to specific cells or tissues were published [9]. Compounds were suggested for liver imaging and enhancing a cardiac infarct [10].

This article reviews the latest developments in making contrast-enhanced MRI even more specific, moving from a tissue characteristic distribution towards molecular imaging.

Section snippets

Liver-specific agents

Extracellular gadolinium (Gd) chelates improve the diagnosis of focal liver lesions. Imaging in the first minutes after injection (‘dynamic phase’) allows a better differential diagnosis but does not always improve the detection rate [11], [12], [13]. As with contrast media (CM)-enhanced computed tomography (CT), gadolinium enhancement patterns reflect the degree of vascularity, flow dynamics and vascular perfusion.

However, the gadolinium enhancement is not really specific to the liver tissue.

Blood-pool agents

MR angiography (MRA) is a perfect example of how imaging technology and imaging diagnostics mature. In the beginning, MRA was clearly an indication without contrast agents. Then, fast imaging technologies were further improved by using relaxation enhancers. Since imaging is still time consuming, compounds that remain in the intravascular space are desirable. However, imaging becomes faster and faster, and the future role of blood-pool agents in MRA is still open. Several paramagnetic and

Gadolinium chelates

Since endolymphatic administration of a substance is an invasive and cumbersome procedure, agents that contrast the lymphatic system after interstitial or intravenous injection are desirable. Various gadolinium-containing formulations contrast the lymphatic vessels and the first lymph nodes (sentinel LN) after an interstitial injection of very low dose. Low-molecular-weight chelates, as well as polymeric agents, also used as blood pool agents, can be used for this indication [95], [96], [97],

Atherosclerotic plaques

New CT and MRI techniques can be used to image atherosclerotic plaques. Detailed information about the status of this systemic disease and the total burden is limited, but MRI studies of the carotid arteries look promising [110], [111], [112], [113], [114], [115], [116]. An imaging modality that could quantify the atherosclerotic plaque burden and composition and the degree of inflammation has the potential to both identify vulnerable atherosclerotic lesions and monitor the effects of

Tumor-specific agents

The clinician's dream of an agent that accumulates highly and specifically in malignant tumors, allowing an accurate diagnosis at a stage when the disease is still treatable, is still far from reality. Studies that describe so called nontoxic, tumor-specific agents are somewhat misleading. Some investigations were performed without relevant controls.

It was suggested that porphyrins or even metalloporphyrins might target tumor cells. Although strong enhancement resulted after the intravenous

Others

The early detection of pancreatic tumors is still a critical issue in diagnostic imaging. It was shown that MnDPDP positively contrasts pancreatic tissue, however, this observation currently has no significant clinical consequences [21], [123], [124], [125], [126]. It is likely that the enhancement is caused by Mn²⁺ released from DPDP, since a binding of free Mn²⁺ to pancreatic tissue has been described in the literature [127], [128], [129].

Most of a specific cell–cell interaction or

Conclusion

Paramagnetic contrast agents have become an integral part of the daily practice of MRI because of their efficacy and their excellent tolerance profile. MRI is very sensitive to the contrast-medium effect, allowing a significant reduction in dose when compared to X-ray technologies. However, using standard contrast materials, such as gadopentetate, gram amounts per patient are still necessary for enhancing brain tumors. Thus, MRI is far less sensitive than either SPECT or PET. New MR agents with

References (158)

J. Barkhausen et al.
Imaging of myocardial infarction: comparison of magnevist and gadophrin-3 in rabbits
J. Am. Coll. Cardiol.
(2002)
H. Hawighorst et al.
Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival
Magma
(1999)
C.R. Leveille-Webster et al.
Use of an asialoglycoprotein receptor-targeted magnetic resonance contrast agent to study changes in receptor biology during liver regeneration and endotoxemia in rats
Hepatology
(1996)
B.K. Schaffer et al.
MION-ASF: biokinetics of an MR receptor agent
Magn. Res. Imaging
(1993)
T. Helmberger et al.
New contrast agents for imaging the liver
Magn. Res. Imaging Clin. North Am.
(2001)
H.-J. Weinmann et al.
Mechanism of hepatic uptake of Gd–EOB-DTPA
Acad. Radiol.
(1996)
L. Pascolo et al.
Molecular mechanisms for the hepatic uptake of magnetic resonance imaging contrast agents
Biochem. Biophys. Res. Commun.
(1999)
A. Spinazzi et al.
Safety, tolerance, biodistribution, and MR imaging enhancement of the liver with gadobenate dimeglumine: results of clinical pharmacologic and pilot imaging studies in nonpatient and patient volunteers
Acad. Radiol.
(1999)
R. Hammerstingl et al.
Contrast-enhanced MRI of focal liver tumors using a hepatobiliary MR contrast agent: detection and differential diagnosis using Gd–EOB-DTPA-enhanced versus Gd–DTPA-enhanced MRI in the same patient
Acad. Radiol.
(2002)
R.B. Lauffer et al.
MS-325: a small-molecule vascular imaging agent for magnetic resonance imaging
Acad. Radiol.
(1996)

F.M. Cavagna et al.

Preclinical profile and clinical potential of gadocoletic acid trisodium salt (B22956/1), a new intravascular contrast medium for MRI

Acad. Radiol.

(2002)

M. Port et al.

P792: a rapid clearance blood pool agent for magnetic resonance imaging: preliminary results

Magma

(2001)

B. Misselwitz et al.

Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent

Magma

(2001)

B. Tombach et al.

First-pass and equilibrium phase MRA following intravenous bolus injection of SH U 555 C: Phase I clinical trial in elderly volunteers with risk factors for arterial vascular disease

Acad. Radiol.

(2002)

B. Misselwitz et al.

Gadofluorine 8: initial experience with a new contrast medium for interstitial MR lymphography

Magma

(1999)

R.J. Kim et al.

Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function

Circulation

(1999)

B. Hofmann et al.

Mechanism of gadophrin-2 accumulation in tumor necrosis

J. Magn. Res. Imaging

(1999)

G. Marchal et al.

Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by MRI

Eur. Radiol.

(1996)

S.H. Heywang et al.

MR imaging of the breast with Gd–DTPA: use and limitations

Radiology

(1989)

W.A. Kaiser et al.

MR imaging of the breast: fast imaging sequences with and without Gd–DTPA. Preliminary observations

Radiology

(1989)

A. Villringer et al.

Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects

Magn. Res. Med.

(1988)

R.B. Lauffer et al.

Iron–EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

J. Comput. Assist. Tomogr.

(1985)

R. Weissleder et al.

Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging

Radiology

(1992)

B. Hamm et al.

Focal liver lesions: characterization with nonenhanced and dynamic contrast material-enhanced MR imaging

Radiology

(1994)

S. Saini et al.

Technique for MR imaging of the liver

Radiology

(1995)

D.L. Rubin et al.

A multicenter, randomized, double-blind study to evaluate the safety, tolerability, and efficacy of OptiMARK (gadoversetamide injection) compared with Magnevist (gadopentetate dimeglumine) in patients with liver pathology: results of a Phase III clinical trial

J. Magn. Res. Imaging

(1999)

R. Weissleder et al.

MR receptor imaging: ultrasmall iron oxide particles targeted to asialoglycoprotein receptors

Am. J. Roentgenol.

(1990)

K.O. Lim et al.

Hepatobiliary MR imaging: first human experience with MnDPDP

Radiology

(1991)

K.G. Toft et al.

Metabolism of mangafodipir trisodium (MnDPDP), a new contrast medium for magnetic resonance imaging, in beagle dogs

Eur. J. Drug Metab. Pharmacokinet.

(1997)

B. Gallez et al.

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

Magn. Res. Med.

(1996)

H. Brurok et al.

Effects of manganese dipyridoxyl diphosphate, dipyridoxyl diphosphate and manganese chloride on cardiac function. An experimental study in the Langendorff perfused rat heart

Invest. Radiol.

(1995)

H.B. Gehl et al.

Mn-DPDP in MR imaging of pancreatic adenocarcinoma: initial clinical experience

Radiology

(1993)

H. Ahlstrom et al.

Overview of MnDPDP as a pancreas-specific contrast agent for MR imaging

Acta Radiol.

(1997)

C. Wang

Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver and pancreas

Acta Radiol. Suppl.

(1998)

M. Oudkerk et al.

Characterization of liver lesions with mangafodipir trisodium-enhanced MR imaging: multicenter study comparing MR and dual-phase spiral CT

Radiology

(2002)

G. Vittadini et al.

B-19036, a potential new hepatobiliary contrast agent for MR proton imaging

Invest. Radiol.

(1988)

H.-J. Weinmann et al.

A new lipophilic gadolinium chelate as a tissue-specific contrast medium for MRI

Magn. Res. Med.

(1991)

G. Schuhmann-Giampieri et al.

Preclinical evaluation of Gd–EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system

Radiology

(1992)

C. Petré et al.

Detection and characterization of primary liver cancer in rats by MS-264-enhanced MRI

Magn. Res. Med.

(1996)

V.M. Runge et al.

A comparison of MR hepatobiliary gadolinium chelates

Am. J. Roentgenol.

(1995)

J.E. van Montfoort et al.

Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1

J. Pharmacol. Exp. Ther.

(1999)

V. Lorusso et al.

Pharmacokinetics and tissue distribution in animals of gadobenate ion, the magnetic resonance imaging contrast enhancing component of gadobenate dimeglumine 0.5 M solution for injection (MultiHance)

J. Comput. Assist. Tomogr.

(1999)

G. Pirovano et al.

Evaluation of the accuracy of gadobenate dimeglumine-enhanced MR imaging in the detection and characterization of focal liver lesions

Am. J. Roentgenol.

(2000)

J. Petersein et al.

Focal liver lesions: evaluation of the efficacy of gadobenate dimeglumine in MR imaging—a multicenter phase III clinical study

Radiology

(2000)

G. Schuhmann-Giampieri et al.

Pharmacokinetics of the liver-specific contrast agent Gd–EOB-DTPA in relation to contrast-enhanced liver imaging in humans

J. Clin. Pharmacol.

(1997)

B. Hamm et al.

Phase I clinical evaluation of Gd–EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging

Radiology

(1995)

S.A. Schmitz et al.

Detection of focal liver lesions: CT of the hepatobiliary system with gadoxetic acid disodium, or Gd–EOB-DTPA

Radiology

(1997)

T.J. Vogl et al.

Liver tumors: comparison of MR imaging with Gd–EOB-DTPA and Gd–DTPA

Radiology

(1996)

P. Reimer et al.

Phase II clinical evaluation of Gd–EOB-DTPA: dose, safety aspects, and pulse sequence

Radiology

(1996)

V.M. Runge et al.

Evaluation of gadolinium 2,5-BPA-DO3A, a new macrocyclic hepatobiliary chelate, in normal liver and metastatic disease on high field magnetic resonance imaging

Invest. Radiol.

(1996)

Cited by (233)

Contrast agents for MRI and side effects
2022, Nuclear Medicine and Molecular Imaging: Volume 1-4
The contrast media most commonly used in MR imaging continues to be Gadolinium chelates. They cause a high magnetic moment of the hydrogen protons of the tissues where they diffuse, determining a reduction in T1 and T2 relaxation times. Gadolinium-DTPA was the first contrast agent to obtain the approval of the pharmacological authorities in 1988. Gadolinium chelates determine a prevalent recovery of the longitudinal magnetization, determining especially a signal enhancement on T1-weighted images, and are defined as paramagnetic contrast media. The ion Gd³⁺ are chelated with organic ligands which may have a linear or macrocyclic structure. Gadolinium-based contrast media, after the intravenous administration, are distributed intra-vascularly and rapidly in the extra-vascular and extra-cellular spaces and then are excreted by the kidneys. In 2008 Systemic Nephrogenic Fibrosis (NSF) was reported in patients who underwent numerous contrast-enhanced MRI examinations. To decrease the risk of NSF, Gadolinium-based contrast agents are contraindicated in patients with hepatic or renal transplantation with GFR less than 60 mL/min/1.73 m², in patients with GFR less than 30 mL/min/1.73 m² and in those with acute renal failure. Adverse reactions to gadolinium are uncommon (incidence: 1.5–2.4%) while acute hypersensitivity reactions occur within 1 h after the administration in about 0.1%. The use of contrast media has undergone considerable development, allowing the use of new technical MRI applications such as brain perfusion based on Dynamic Susceptibility Contrast (DSC) technique, Late Enhancement technique for the study of damaged myocardium, Dynamic Contrast Enhancement (DCE) with T1-weighted sequences fundamental in the study of breast cancer. The advent of hepato-specific contrast media also have allowed further extension in the clinical indications of abdominal MRI. The predictable development of new contrast media with greater relaxivity will raise their use in the clinical practice, allowing one to obtain drugs targeted to specific pathology and to monitor the therapeutic response.
Magnetic Resonance Imaging Agents
2021, Molecular Imaging: Principles and Practice
This chapter introduces the fundamental principles of how magnetic resonance imaging (MRI) agents work, and the progress in molecular MRI agent development and applications in three major categories: gadolinium-based contrast agents (GBCAs), superparamagnetic iron oxide (SPIO) nanoparticles, and chemical exchange saturation transfer (CEST) agents. These agents are designed to bind to biological and pathological targets or be responsive to enzyme activities, pH changes, or metabolites. The interactions of these agents with targets and environment result in increased relaxivity and improved specificity and efficiency compared to conventional nonspecific contrast agents. Translation of molecular MRI agents will likely usher in a new era of highly specific and sensitive imaging of human physiology and pathology with unprecedented detail to advance diagnosis, therapy development, and treatment monitoring.
Nanotheranostics: Their role in hepatocellular carcinoma
2020, Critical Reviews in Oncology/Hematology
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide. Despite advances in imaging techniques, early diagnosis and management remain very poor. The early diagnosis of HCC requires diagnostic and imaging technologies with high sensitivity and precise quantification ability and with no tissue penetration limit. Nanotechnology-based cancer imaging is a rapidly emerging research area with significant applications in the diagnosis and treatment of cancer, which we review here with application to HCC. Furthermore, we discuss the combination of functional nanotheranostics and magnetic resonance imaging (MRI) for targeted delivery of phytochemical therapeutics, chemotherapeutic drugs, RNAi-based therapeutics, and vaccinations. Finally, this review presents the importance of MRI biomarkers for monitoring HCC treatment response. The use of advanced nanotheranostics as MRI contrast agents for imaging, diagnosis and drug delivery may enhance HCC management and provide a new area of research in tumor imaging technology.
Inorganic and organic-inorganic composite nanoparticles with potential biomedical applications: Synthesis challenges for enhanced performance
2019, Materials for Biomedical Engineering: Bioactive Materials, Properties, and Applications
Methods to obtain inorganic and organic–inorganic composite nanoparticles (NP) have been investigated for the past few decades aiming at biomedical applications due to their unique properties and finite size. Although many attempts to synthesize and test NPs for biomedicine have been made, there are still challenges to achieve inorganic or organic–inorganic composite NPs with controlled morphology and improved properties. Recent advances concerning synthesis, individual, and synergistic properties in hybrid systems as well as some aspects of functionalization and biocompatibilization are discussed in this chapter. Nanoparticles with magnetic and optical properties are being tested for diagnosis and therapy of diseases. Nanocomposites, heterostructures of inorganic materials, can unify both properties leading to theranostic NPs. In addition to the properties of inorganic NPs an organic shell must be used to decrease toxicity of naked NPs. Different organic molecules can be used as surface linkers and coatings to provide the additional biofunctionalization, such as a target agent. Carbon-based inorganic nanostructures including carbon-dots, graphene oxide, reduced graphene oxide, graphene, carbon nanotubes, fullerene, and others are not discussed in this chapter.
Visualization of Arc promoter-driven neuronal activity by magnetic resonance imaging
2018, Neuroscience Letters
Visualization of direct neuronal activity to understand brain function is one of the most important challenges in neuroscience. We have previously demonstrated that in vivo and in vitro gene expression of the ferritin reporter system could be detected by magnetic resonance imaging (MRI). In addition, increased neuronal activity induces Arc, an immediate early gene, and insertion of a destabilized fluorescent reporter dVenus under Arc promoter control has been used for monitoring neuronal activities in the brain by optical imaging. In this study, to visualize Arc promoter-driven neuronal activities directly, we generated transgenic mice and cell lines that express a destabilized fusion reporter ferritin-mKate2 under Arc promoter control. When transgenic mice and cell lines were treated with pilocarpine, a non-selective muscarinic agonist, an increase in T2-weighted image signal was successfully found in neuronal cells. There was a difference in peak time between MRI and fluorescence imaging, which might result from the binding process of iron with ferritin. Visualization of Arc promoter-driven neuronal activity is essential to understand neural mechanisms underlying cognitive processes and complex behaviors, and could be a useful tool for therapeutic approaches in the brain by MRI.
Magnetoliposomes for dual cancer therapy
2018, Inorganic Frameworks as Smart Nanomedicines
Liposomes can overcome many of the problems associated with other systems used in therapy, such as problems involving solubility, toxicity, pharmacokinetics, and in vivo stability. However, this system still presents some issues for in vivo application, namely its recognition and capture by the immune system and the location in therapeutic sites for drug release. In order to overcome these problems, magneto-sensitive liposomes have been proposed. The magnetic components allow the concentration of the liposomes in the desired area of the patient organs by magnetic forces. Therefore, a new therapy is emerging, involving the magnetically guided transport of drugs (most of them toxic and with systemic side effects), and focusing them in specific sites of the human body.
Magneto-sensitive liposomes result from the encapsulation of magnetic nanoparticles into liposomes. The so-called magnetoliposomes combine the amazing physical properties of these two types of nanosystems and preserve the magnetic properties of the nanoparticles. This ideal nanocarrier can be used in a wide array of biomedical applications. In therapy, the most promising applications of magnetoliposomes are magnetic-guided drug delivery and hyperthermia. Furthermore, in diagnosis, magnetic nanoparticles have been used as contrast agents in magnetic resonance imaging.
The magnetic nanoparticles can be either entrapped in liposomes, creating aqueous magnetoliposomes, or covered with a lipid bilayer, forming solid (or dry) magnetoliposomes. Both aqueous and solid magnetoliposomes have been used as nanocarriers for new and well-established anticancer drugs.
This chapter describes the synthesis, characterization, and applications of magnetoliposomes in cancer therapy, both by antitumor drug delivery and hyperthermia, as well as the ability to attain magnetic guidance to the therapeutic sites of interest.

View all citing articles on Scopus

View full text

Review articleTissue-specific MR contrast agents

Abstract

Introduction

Section snippets

Liver-specific agents

Blood-pool agents

Gadolinium chelates

Atherosclerotic plaques

Tumor-specific agents

Others

Conclusion

J. Am. Coll. Cardiol.

Magma

Hepatology

Magn. Res. Imaging

Magn. Res. Imaging Clin. North Am.

Acad. Radiol.

Biochem. Biophys. Res. Commun.

Acad. Radiol.

Acad. Radiol.

Acad. Radiol.

Acad. Radiol.

Magma

Magma

Acad. Radiol.

Magma

Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function

Circulation

Mechanism of gadophrin-2 accumulation in tumor necrosis

J. Magn. Res. Imaging

Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by MRI

Eur. Radiol.

MR imaging of the breast with Gd–DTPA: use and limitations

Radiology

MR imaging of the breast: fast imaging sequences with and without Gd–DTPA. Preliminary observations

Radiology

Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects

Magn. Res. Med.

Iron–EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

J. Comput. Assist. Tomogr.

Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging

Radiology

Focal liver lesions: characterization with nonenhanced and dynamic contrast material-enhanced MR imaging

Radiology

Technique for MR imaging of the liver

Radiology

A multicenter, randomized, double-blind study to evaluate the safety, tolerability, and efficacy of OptiMARK (gadoversetamide injection) compared with Magnevist (gadopentetate dimeglumine) in patients with liver pathology: results of a Phase III clinical trial

J. Magn. Res. Imaging

MR receptor imaging: ultrasmall iron oxide particles targeted to asialoglycoprotein receptors

Am. J. Roentgenol.

Hepatobiliary MR imaging: first human experience with MnDPDP

Radiology

Metabolism of mangafodipir trisodium (MnDPDP), a new contrast medium for magnetic resonance imaging, in beagle dogs

Eur. J. Drug Metab. Pharmacokinet.

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

Magn. Res. Med.

Effects of manganese dipyridoxyl diphosphate, dipyridoxyl diphosphate and manganese chloride on cardiac function. An experimental study in the Langendorff perfused rat heart

Invest. Radiol.

Mn-DPDP in MR imaging of pancreatic adenocarcinoma: initial clinical experience

Radiology

Overview of MnDPDP as a pancreas-specific contrast agent for MR imaging

Acta Radiol.

Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver and pancreas

Acta Radiol. Suppl.

Characterization of liver lesions with mangafodipir trisodium-enhanced MR imaging: multicenter study comparing MR and dual-phase spiral CT

Radiology

B-19036, a potential new hepatobiliary contrast agent for MR proton imaging

Invest. Radiol.

A new lipophilic gadolinium chelate as a tissue-specific contrast medium for MRI

Magn. Res. Med.

Preclinical evaluation of Gd–EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system

Radiology

Detection and characterization of primary liver cancer in rats by MS-264-enhanced MRI

Magn. Res. Med.

A comparison of MR hepatobiliary gadolinium chelates

Am. J. Roentgenol.

Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1

J. Pharmacol. Exp. Ther.

Pharmacokinetics and tissue distribution in animals of gadobenate ion, the magnetic resonance imaging contrast enhancing component of gadobenate dimeglumine 0.5 M solution for injection (MultiHance)

J. Comput. Assist. Tomogr.

Review article
Tissue-specific MR contrast agents