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

Hamm, Bernd; Staks, Thomas; Mühler, Andreas; Bollow, Matthias; Taupitz, Matthias; Frenzel, Thomas; Wolf, K. J.; Weinmann, Hanns‐Joachim; Lange, L

doi:10.1148/radiology.195.3.7754011

Cited by 526 publications

(389 citation statements)

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“…Previous studies have demonstrated that Gd-EOB-DTPA is well tolerated and has no substantial adverse events and minor adverse events of 5.9% (6,7,19). In fact, there were no severe adverse effects in our study population.…”

Section: Discussionsupporting

confidence: 50%

Dynamic contrast‐enhanced magnetic resonance imaging of abdominal solid organ and major vessel: Comparison of enhancement effect between Gd‐EOB‐DTPA and Gd‐DTPA

Tamada

Ito

Sone

et al. 2009

Magnetic Resonance Imaging

109

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Purpose:To evaluate the differences in enhancement of the abdominal solid organ and the major vessel on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) obtained with gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA: EOB) and gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) in the same patients. Materials and Methods:A total of 13 healthy volunteers underwent repeat assessments of abdominal MR examinations with DCE-MRI using either Gd-DTPA at a dose of 0.1 mmol/kg body weight or EOB at a dose of 0.025 mmol/kg body weight. DCE images were obtained at precontrast injection and in the arterial phase (AP: 25 seconds), portal phase (PP: 70 seconds), and equilibrium phase (EP: 3 minutes). The signal intensities (SIs) of liver at AP, PP, and EP; the SIs of spleen, renal cortex, renal medulla, pancreas, adrenal gland, aorta at AP; and the SIs of portal vein and inferior vena cava (IVC) at PP were defined using region-ofinterest measurements, and were used for calculation of signal intensity ratio (SIR). There was no significant difference in mean SIR of liver at PP between EOB (0.529 Ϯ 0.124) and Gd-DTPA (0.564 Ϯ 0.139). Conversely, the mean SIR of liver at EP was significantly higher with EOB (0.576 Ϯ 0.167) than with Gd-DTPA (0.396 Ϯ 0.093) (P Ͻ 0.001). Results Conclusion:Lower arterial vascular and parenchymal enhancement with Gd-EOB, as compared with Gd-DTPA, may require reassessment of its dose, despite the higher late venous phase liver parenchymal enhancement.

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Section: Discussionsupporting

confidence: 50%

Dynamic contrast‐enhanced magnetic resonance imaging of abdominal solid organ and major vessel: Comparison of enhancement effect between Gd‐EOB‐DTPA and Gd‐DTPA

Tamada

Ito

Sone

et al. 2009

Magnetic Resonance Imaging

109

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“…This contrast agent is highly liver-specific; approximately 50% of the injected dose is taken up by functioning hepatocytes and is excreted in bile, as compared to an uptake of 3-5% for gadobenate dimeglumine (4). A bolus injection of gadoxetic acid provides a dual mode of action that allows imaging in the early dynamic phase (as with standard gadolinium chelates) and in the delayed phase (hepatobiliary phase) that is obtained 10 to 20 min after injection and lasts until 90 min after injection (7,8). In the hepatobiliary phase, malignant hepatic lesions lacking normally functioning hepatocytes are imaged as a defect of hepatocyte-selective enhancement as compared to the normal parenchyma (9).…”

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confidence: 99%

Comparison between areas with Gd‐EOB‐DTPA uptake and without in hepatocellular carcinomas on Gd‐EOB‐DTPA‐enhanced hepatobiliary‐phase MR imaging: Pathological correlation

Lee

Kim

Park

et al. 2010

Magnetic Resonance Imaging

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Purpose: To determine histological and MR imaging differences between areas with Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid) uptake and without in hepatocellular carcinomas (HCCs) as seen on Gd-EOB-DTPA-enhanced hepatobiliary-phase MR images. Materials and Methods:This study included nine patients with nine histopathologically proven HCCs (mean size, 1.9 cm) that consisted of two portions of a non-hypointense (Gd-EOB-DTPA uptake) and hypointense area (no Gd-EOB-DTPA uptake) in one tumor as depicted on hepatobiliary-phase MR images. Two radiologists and one pathologist compared the histological and MR finding differences between the two portions in consensus.Results: In eight specimens, non-hypointense areas of six specimens showed a green color and two specimens did not show a green color. Microscopically, two of nine showed a higher percentage of bile pigments in the nonhypointense area as compared to the hypointense area and the remaining seven showed no difference. Six were homogeneous Edmondson-Steiner grade II, and one was grade I. In two, non-hypointense areas were grade II and hypointense areas were grade I. No difference between the two portions was found for necrosis, hemorrhage, fibrosis, and a fibrous capsule. Seven on T1/T2-weighted images and eight on arterial and portal phase images showed no different signal intensity between the two portions. Conclusion:Although macroscopically, a non-hypointense area of an HCC seen on GD-EOB-DTPA-enhanced hepatobiliary-phase images may be associated with the area with a green color, no definite microscopic and MR imaging findings that could discriminate a non-hypointense from a hypointense area of an HCC was found.

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“…The rest is eliminated by the kidneys. Due to the low hepatic absorption, Gd-BOPTA has not been able to become a relevant imaging-based liver function test [13,39]. Like mebrofenin, Gd-EOB is absorbed by the hepatocytes via organic anion-transporting polypeptides (OATP) 1B1 and 1B3 and is then eliminated in bile via multidrug resistance protein (MRP) 2 [39 -42].…”

Section: Mri As Imaging-based Liver Function Testmentioning

confidence: 99%

Imaging-Based Liver Function Tests – Past, Present and Future

Geisel

Lüdemann

Hamm

et al. 2015

Fortschr Röntgenstr

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Preoperative assessment of liver function and?prediction of postoperative functional reserve are important in patients scheduled for liver resection. While determination of absolute liver function currently mostly relies on laboratory tests and clinical scores, postoperative remnant liver function is estimated volumetrically using imaging data obtained with computed tomography (CT) or magnetic resonance imaging (MRI). Accurate estimation of hepatic function is also relevant for intensive care patients, oncologic patients, and patients with diffuse liver disease. The indocyanine green (ICG) test is still the only established test for estimating true global liver function. However, more recent tools such as the LiMAx test also allow global assessment of hepatic function. These tests are limited when liver function is inhomogeneously distributed, which is the case in such conditions as unilateral cholestasis or after portal vein embolization. Imaging-based liver function tests were first developed in nuclear medicine and, compared with laboratory tests, have the advantage of displaying the spatial distribution of liver function. Nuclear medicine scans are obtained using tracers such as?99mTc galactosyl and 99mTc mebrofenin. Liver function is typically assessed using planar scintigraphy. However, three-dimensional volumetry is possible with single-photon emission computed tomography (SPECT-CT). Another technique for image-based liver function estimation is Gd-EOB-enhanced MRI. While metabolization of Gd-EOB in the body is similar to that of ICG and mebrofenin, its distribution in the liver can be displayed by MRI with higher temporal and spatial resolution. Moreover, MRI-based determination of liver function can be integrated into routine preoperative imaging. This makes MRI an ideal candidate for preoperative determination of?liver function, though the best pulse sequence and the parameter to be derived from the image information remain to be identified. Another question to be answered is how the results may be affected by renal function and the presence of hyperbilirubinemia. As more results from clinical evaluation including comparison with postoperative liver function data become available, image-based liver function tests, especially with use of Gd-EOB as the contrast medium, have the potential to add another dimension to preoperative imaging. Key Points: ??Liver function consists of a multitude of subfunctions such as biotransformation, excretion and storage. ??Global liver function tests are score-based tests such as Child-Pugh or MELD as well as the ICG- and LiMAx-test. ??Imaging-based liver function tests add spatial information. Current clinical standard is the 99mTc-Mebrofenin-scintigraphy. ??MRI-based function tests with Gd-EOB-DTPA have the potential to integrate seamlessly into clinical workup, feature a higher temporal and spatial resolution and do not rely on ionizing radiation. Citation Format: ??Geisel D, L?demann L, Hamm B et?al. Imaging-Based Liver Function Tests ? Past, Present and F...

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

Abstract: Gd-EOB-DTPA is safe and efficient for MR imaging of the liver.

Cited by 526 publications

References 0 publications

Dynamic contrast‐enhanced magnetic resonance imaging of abdominal solid organ and major vessel: Comparison of enhancement effect between Gd‐EOB‐DTPA and Gd‐DTPA

Dynamic contrast‐enhanced magnetic resonance imaging of abdominal solid organ and major vessel: Comparison of enhancement effect between Gd‐EOB‐DTPA and Gd‐DTPA

Comparison between areas with Gd‐EOB‐DTPA uptake and without in hepatocellular carcinomas on Gd‐EOB‐DTPA‐enhanced hepatobiliary‐phase MR imaging: Pathological correlation

Imaging-Based Liver Function Tests – Past, Present and Future

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