gadoxetic-acid-disodium and gadofosveset-trisodium

Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

Topics: Animals; Contrast Media; Gadolinium; Gadolinium DTPA; Heterocyclic Compounds; Humans; Meglumine; Nephrogenic Fibrosing Dermopathy; Organometallic Compounds; Terminology as Topic

MRI offers an alternative to CT, and thus is central to an ALARA strategy. However, long exam times, limited magnet availability, and motion artifacts are barriers to expanded use of MRI. This article reviews developments in pediatric body MRI that might reduce these barriers: high field systems, acceleration, navigation and newer contrast agents.

Topics: Abdomen; Artifacts; Cardiovascular System; Child; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Image Enhancement; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Organometallic Compounds; Pediatrics; Pelvis

The objective or our study was to assess the incidence rate and clinical characteristics of allergiclike reactions in patients who received both nonionic iodinated contrast medium (ICM) and gadolinium-based contrast medium (GBCM).. Acute allergiclike reactions in patients who received both ICM and GBCM to nonionic ICM or GBCM injections during a 5-year period were analyzed. Allergy preparation was not administered when patients received a different type of contrast material. Acute allergiclike reactions to both ICM and GBCM were evaluated.. Of 302,858 contrast injections (155,234 ICM and 147,624 GBCM) during a 5-year period, 1006 (752 ICM and 254 GBCM) acute allergiclike contrast reactions were reported. The overall rate of reaction to ICM was 0.48% (95% CI, 0.45-0.52%), and the overall rate of reaction to GBCM was 0.17% (95% CI, 0.15-0.19%). A total of 19,237 patients received at least one ICM injection and one GBCM injection, with a total of 56,310 injections (19,237 initial injections and 37,073 subsequent injections). Nine patients had reactions to both ICM and GBCM with the primary reaction rate of 9/19,237 (incidence rate, 0.047%; 95% CI, 0.044-0.050%), and the secondary reaction rate of 9/37,073 (incidence rate, 0.024%; 95% CI, 0.023-0.026%). All secondary reactions in patients who had a reaction to both ICM and GBCM were mild. None of the patients required medication for the treatment of the secondary reaction.. An allergiclike reaction to both nonionic ICM and GBCM was an extremely rare event that presented as a mild acute reaction without significant clinical consequences despite the fact that an allergy preparation was not administered.

Topics: Adult; Aged; Aged, 80 and over; Contrast Media; Drug Hypersensitivity; Female; Gadolinium; Gadolinium DTPA; Humans; Incidence; Iodine; Male; Meglumine; Middle Aged; Organometallic Compounds; Retrospective Studies; Risk Factors

To compare gadoxetic acid alone and combined gadoxetic acid/gadofosveset trisodium-enhanced liver MRI for detection of metastases and differentiation of metastases from haemangiomas.. Ninety-one patients underwent gadoxetic acid-enhanced liver MRI before and after additional injection of gadofosveset. First, two readers retrospectively identified metastases on gadoxetic acid alone enhanced delayed hepatobiliary phase T1-weighted images together with all other MR images (dynamic images, T2-weighted images, diffusion-weighted images). Second, readers assessed additional T1-weighted images obtained after administration of gadofosveset trisodium. For both interpretations, readers rated lesion conspicuity and confidence in differentiating metastases from haemangiomas. Results were compared using alternative free-response receiver-operating characteristic (AFROC) and conventional ROC methods. Histology and follow-up served as reference standard.. There were 145 metastases and 16 haemangiomas. Both readers detected more metastases using combined gadoxetic acid/gadofosveset (reader 1 = 130; reader 2 = 124) compared to gadoxetic acid alone (reader 1 = 104; reader 2 = 103). Sensitivity of combined gadoxetic acid/gadofosveset (reader 1 = 90 %; reader 2 = 86 %) was higher than that of gadoxetic acid alone (reader 1 = 72 %; reader 2 = 71 %, both P < 0.01). AFROC-AUC was higher for the combined technique (0.92 vs. 0.86, P < 0.001). Sensitivity for correct differentiation of metastases from haemangiomas was higher for the combined technique (reader 1 = 98 %; reader 2 = 99 % vs. reader 1 = 86 %; reader 2 = 91 %, both P < 0.01). ROC-AUC was significantly higher for the combined technique (reader 1 = 1.00; reader 2 = 1.00 vs. reader 1 = 0.87; reader 2 = 0.92, both P < 0.01).. Combined gadoxetic acid/gadofosveset-enhanced MRI improves detection and characterization of liver metastases compared to gadoxetic acid alone.. • Combined gadoxetic acid and gadofosveset-enhanced liver MRI significantly improves detection of metastases. • The combined enhancement technique improves the accuracy to differentiate metastases from haemangiomas. • Prospective studies need to determine the clinical impact of the combined technique.

Topics: Contrast Media; Female; Gadolinium; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Organometallic Compounds; Prospective Studies; Retrospective Studies; ROC Curve

Demonstration of feasibility and protocol optimization for the combined use of gadofosveset trisodium with gadoxetic acid for delayed T1-weighted liver MRI.. Eleven healthy volunteers underwent hepatobiliary phase imaging at 3 Tesla (T) using gadoxetic acid. Multiple breathheld T1-weighted three-dimensional spoiled gradient echo sequences were performed at varying flip angles before and after injection of gadofosveset. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured to determine optimal T1-weighting. Examples of three patients with focal liver lesions were acquired.. The addition of gadofosveset to the hepatobiliary phase of gadoxetic acid renders vessels isointense to liver tissue at low flip angles due to increased vessel SNR (P < 0.001). The lowest CNR of liver relative to portal vein (CNR = 15; 95% confidence interval [CI]: -14-44) was observed at a 10º flip angle. The highest CNR of liver relative to muscle (CNR = 214; 95% CI: 191-237) was observed at a 20º flip angle. The combined enhancement leads to homogenously enhanced liver tissue and liver vasculature. Cysts were detected in three volunteers and metastases were detected in two patients. In these anecdotal cases the cysts and metastases stood out as conspicuous focal hypointensities on combined gadoxetic acid and gadofosveset enhanced images.. Combined gadoxetic acid and gadofosveset enhanced liver MRI is feasible, with low flip angles minimizing contrast between vessels and liver. Further clinical studies are needed to confirm that low flip angles provide an optimal combination of sensitivity and specificity for lesion detection in patients.

Topics: Adult; Contrast Media; Drug Combinations; Drug Synergism; Feasibility Studies; Female; Gadolinium; Gadolinium DTPA; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Organometallic Compounds; Reproducibility of Results; Sensitivity and Specificity; Young Adult

To report the authors' experience with the administration of four gadolinium-based contrast agents (GBCA; gadopentetate dimeglumine, gadofosveset trisodium, gadoxetate disodium and gadobenate dimeglumine) in a large study population at a single, large academic medical centre.. The institutional review board approved this retrospective study in which data in the electronic incident reporting system were searched. A total of 194, 400 intravenous administrations of linear ionic GBCAs were assessed for the incidence of adverse reactions and risk factors from 1 January 2007 to 14 January 2014. The severity of reactions (mild, moderate, and severe), patient type (outpatients, inpatients, and emergency), examination type, and treatment options were also investigated.. In total, 204/194400 (0.1%) patients (mean age 45.7 ± 14.9) showed adverse reactions, consisting of 6/746 (0.80%), 10/3200 (0.31%), 14/6236 (0.22%) and 174/184218 (0.09%), for gadofosveset trisodium, gadoxetate disodium, gadobenate dimeglumine, and gadopentetate dimeglumine, respectively. An overall significant difference was found between different GBCAs regarding the total number of reactions (p < 0.0001). When comparing the GBCAs together, significant differences were found between gadofosveset trisodium versus gadopentetate dimeglumine (p < 0.0001), gadofosveset trisodium versus gadobenate dimeglumine (p = 0.0051), gadoxetate disodium versus gadopentetate dimeglumine (p < 0.0001) and gadopentetate dimeglumine versus gadobenate dimeglumine (p = 0.0013). Rate of reaction was higher in females (F: 146/113187, 0.13%/M: 58/81213, 0.07%; p < 0.0001). Rate of reactions was higher in outpatient (180/158885, 0.11%), emergency (10/10413, 0.10%), and inpatients (14/25102, 0.05%), respectively (p < 0.0001). Most of the patients had mild symptoms 171/204 (83.8%). Abdomen-pelvis, liver, and thoracic examinations had highest rates of reactions (0.17 versus 0.16 versus 0.15).. The overall rate of adverse reaction to GBCAs was 0.1%. The rates of reactions were highest in gadofosveset trisodium with (0.80%), followed by gadoxetate disodium (0.31%), gadobenate dimeglumine (0.22%) and gadopentetate dimeglumine (0.09%).

Topics: Adult; Adverse Drug Reaction Reporting Systems; Contrast Media; Drug Hypersensitivity; Female; Gadolinium; Gadolinium DTPA; Humans; Injections; Male; Meglumine; Middle Aged; Organometallic Compounds; Retrospective Studies; Risk Factors; Severity of Illness Index; Sex Factors

To intraindividually compare gadoxetate disodium and gadofosveset trisodium regarding vessel contrast, image quality and vessel delineation in dynamic contrast-enhanced liver MRI at 3.0T.. Twelve patients underwent 3.0T MRI twice (24 examinations) with a single dose of gadoxetate disodium and gadofosveset trisodium, respectively. Signal intensity in abdominal vessels and tissue was determined. Vessel-to-background ratio (VBR) was calculated for each vessel and dynamic phase. All images were evaluated by two radiologists regarding image quality, vessel delineation and anatomic variants or pathologies with digital subtraction angiography as the standard of reference.. Gadofosveset trisodium demonstrated a significantly higher VBR compared to gadoxetate disodium (arterial phase: 0.57±0.12 [SD] vs. 0.46±0.19; portal venous phase: 0.51±0.11 vs. 0.37±0.14; equilibrium phase: 0.48±0.10 vs. 0.31±0.13; p≤0.01). Image quality and vessel delineation were rated equal or better for gadofosveset trisodium in all cases. These differences were not significant for most vessel segments. All anatomic variants were correctly identified by both readers for both contrast agents.. Although gadofosveset trisodium provides a significantly higher vessel contrast at 3.0T, gadoxetate disodium is equivalent by qualitative measurements. Thus, gadoxetate-enhanced liver MRI at 3.0T enables reliable assessment of the upper abdominal vasculature with the additional benefit of hepatobiliary imaging.

Topics: Aged; Angiography, Digital Subtraction; Contrast Media; Female; Gadolinium; Gadolinium DTPA; Humans; Image Enhancement; Liver; Magnetic Resonance Imaging; Male; Middle Aged; Organometallic Compounds; Reproducibility of Results

The objective of this study was to measure the protein-specific response of r1 and r2 relaxivities of commercially available gadolinium-based magnetic resonance imaging contrast agents to variation of plasma-protein concentrations.. In this in vitro study, contrast agent (gadofosveset trisodium, gadoxetate disodium, gadobutrol, and gadoterate meglumine) dilution series (0-2.5 mmol Gd/L) were prepared with plasma-protein (human serum albumin [HSA] and immunoglobulin G [IgG]) concentrations at physiological (42 and 10 g/L HSA and IgG, respectively, Normal) and at 3 pathological levels with HSA/IgG concentrations of 10/10 (solution Alb low), 42/50 (IgG mild), and 42/70 (IgG severe) g/L. Contrast-agent molar relaxivities and relaxivity-enhancing protein-contrast-agent interaction coefficients were determined on the basis of inversion-recovery and spin-echo data acquired at 1.5 and 3.0 T at 37°C. Protein-induced magnetic resonance imaging signal changes were calculated.. The effective r1 and r2 molar relaxivities consistently increased with albumin and IgG concentrations. At 1.5 T, the r1 values increased by 10.2 (gadofosveset), 4.3 (gadoxetate), 1.3 (gadobutrol), and 1.1 L s mmol (gadoterate), respectively, from the Alb low to the IgG severe solution. At 3.0 T, the r1 values increased by 2.9 (gadofosveset), 2.3 (gadoxetate), 0.7 (gadobutrol), and 0.9 (gadoterate) L s mmol, respectively. An excess of IgG most strongly increased the r1 of gadoxetate (+40 and +19% at 1.5 and 3.0 T, respectively, from Normal to IgG severe). An albumin deficiency most strongly decreased the r1 of gadofosveset (-44% and -20% at 1.5 and 3.0 T, respectively, from Normal to Alb low). The modeling confirmed a strong gadofosveset r1 enhancement by albumin and suggested stronger IgG than albumin effects on the apparent molar relaxivity of the other agents per protein mass concentration at 1.5 T.. Pathological deviations from normal plasma-protein concentrations in aqueous solutions result in changes of effective r1 and r2 contrast-agent relaxivities and projected signal enhancements that depend on the contrast agent, the blood-serum protein profile, and the field strength.

Topics: Blood Proteins; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Meglumine; Organometallic Compounds; Proteins

Enhanced nonenzymatic glycosylation (NEG) of human serum albumin (HSA) is observed in diabetic patients. This modifies some of the physiological functions of HSA, as the binding of ligands. Some gadolinium complexes, commonly used as MRI contrast agents, have a high affinity for HSA, which enhances their efficacy. The aim of this study is to evaluate the possible influence of the NEG of HSA on its affinity for some gadolinium chelates.

Topics: Chelating Agents; Contrast Media; Diabetes Mellitus; Gadolinium; Gadolinium DTPA; Glycosylation; Humans; Nuclear Magnetic Resonance, Biomolecular; Organometallic Compounds; Serum Albumin