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

PURPOSE: To evaluate gadobenate dimeglumine (Gd-BOPTA) for dynamic and delayed magnetic resonance (MR) imaging of focal liver lesions. MATERIALS AND METHODS: In 126 of 214 patients, MR imaging was performed before Gd-BOPTA administration, immediately after bolus administration of a 0.05- mmol/kg dose of Gd-BOPTA, and 60-120 minutes after an additional intravenously infused 0.05-mmol/kg dose. In 88 patients, imaging was performed before and 60-120 minutes after a single, intravenously infused 0.1-mmol/kg dose. T1- and T2-weighted spin-echo and T1-weighted gradient-echo images were acquired. On-site and blinded off-site reviewers prospectively evaluated all images. Intraoperative ultrasonography, computed tomography (CT) during arterial portography, and/or CT with iodized oil served as the reference methods in 110 patients. RESULTS: Significantly more lesions were detected on combined pre- and postcontrast images compared with on precontrast images alone (P <. 01). All reviewers reported a decreased mean size of the smallest detected lesion and improved lesion conspicuity on postcontrast images. All on-site reviewers and two off-site reviewers reported increased overall diagnostic confidence (P <.01). Additional lesion characterization information was provided on up to 109 (59%) of 184 delayed images and for up to 50 (42%) of 118 patients in whom dynamic images were assessed. Gd-BOPTA would have helped change the diagnosis in 99 (47%) of 209 cases and affected patient treatment in 408 (23%) of 209 cases. CONCLUSION: Gd-BOPTA increases liver lesion conspicuity and detectability and aids in the characterization of lesions.     

Neurotolerability of gadobenate dimeglumine in a rat model of focal brain ischemia: EEG evaluation

RATIONALE AND OBJECTIVES: The neurologic pathologies for which contrast-enhanced MRI is indicated are often accompanied by a disruption of the blood-brain barrier (BBB), which allows the contrast agent to come into contact with the nervous tissue. Thus, assessment of the neurologic safety for a new contrast agent is of crucial importance. The objective of this study was to assess the neurotolerability of the new MRI contrast agent gadobenate dimeglumine using EEG in the presence of focal lesions of the BBB. METHODS: Lesions of the BBB were obtained inducing a photochemical ischemia in rats. Gadobenate dimeglumine was intravenously administered at 4.0 mmol/kg. An EEG was recorded during sleep/awake behavior and was analyzed for pathologic tracing and for changes in spectral content in terms of total power and frequency index. The presence of the BBB lesions was verified using high-performance liquid chromatography measurement of the gadobenate ion content in the brain. RESULTS: Gadobenate dimeglumine did not have any epileptogenic effect in ischemic rats. However, it caused a transitory shift of the EEG power spectrum toward the 0.5 to 9 Hz frequency bands of the lesioned hemisphere during quiet wake. In the lesioned cortex, higher levels of gadobenate ion were found until 3 hours after administration. CONCLUSIONS: In experimental conditions of focal brain ischemia associated with BBB lesions, gadobenate dimeglumine was well tolerated up to doses even 10 times higher than the maximum clinical dose (0.3 mmol/kg) intended for brain imaging procedures.     

钆贝酸二葡甲胺与钆喷酸葡胺乳腺MRI的多中心、双盲、随机、个体间交叉对照研究(检出实验)

目的利用前瞻性、多中心双盲随机数据对0.1mmol/kg剂量的钆贝酸二葡甲胺与钆喷酸葡胺对比剂增强乳腺MRI行个体间对照研究。材料与方法研究经学院评     

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

PURPOSE: The purpose of this study was to assess safety, tolerance, biodistribution, and magnetic resonance (MR) imaging enhancement of the liver with gadobenate dimeglumine. MATERIALS AND METHODS: Phase I single-blind studies were performed in 53 healthy volunteers, of whom 39 received gadobenate dimeglumine and 14 placebo. Another 106 patients with focal liver disease received gadobenate dimeglumine in parallel-group, open-label, phase II studies. The imaging potential of gadobenate dimeglumine was assessed in all 106 patients plus 11 healthy volunteers, whereas pharmacokinetics were determined for 42 healthy volunteers. Safety was assessed for all subjects enrolled in the study. Imaging protocols for healthy volunteers were similar to those for patients and comprised predose T2-weighted sequences and pre- and postinjection T1-weighted spin-echo and gradient-echo sequences. RESULTS: Gadobenate dimeglumine was safe and well tolerated in healthy volunteers and patients, with pharmacokinetics described adequately as a distribution phase and an elimination phase. Most of the injected dose of gadobenate was excreted unchanged in urine within 24 hours, although a fraction corresponding to 0.6%-4.0% of the injected dose was eliminated with the bile and recovered in the feces. The gadobenate dimeglumine-enhanced signal intensity of liver parenchyma was dose-related and constant for 120 minutes. Gadobenate dimeglumine-enhanced MR imaging was superior to nonenhanced MR imaging in more than 50% of patient studies, with more lesions seen in 26%-38% of patients and smaller lesions in 21%-33% of patients. In general, image sets acquired 40-180 minutes after administration of a dose were preferred, whereas images acquired during the dynamic phase after administration were typical of those obtained with extracellular fluid contrast agents. CONCLUSION: Gadobenate dimeglumine is a safe and efficacious MR imaging contrast agent suitable for both delayed and dynamic imaging of the liver.     

Phase III, randomized, double-blind, cross-over comparison of gadoteridol and gadopentetate dimeglumine in magnetic resonance imaging of patients with intracranial lesions

This study compares the efficacy and safety of gadoteridol with that of gadopentetate dimeglumine for enhanced MRI in subjects with intracranial lesions. A total of 92 subjects at three European centres underwent one MRI study enhanced with 0.1 mmol/kg gadoteridol and another with 0.1 mmol/kg gadopentetate dimeglumine. Contrast agents were assigned in random order, separated by 3-7 days. Eighty subjects were evaluated for efficacy. The presence of pathology, degree of enhancement, location and number of lesions, as well as additional information gained, were compared for each subject's unenhanced and enhanced scans for both the gadoteridol and gadopentetate dimeglumine examination. Safety was evaluated in all treated subjects by means of pre- and post-dose vital signs, laboratory tests and by monitoring for adverse events. There was no significant difference in the number of lesions visualized pre- and post-contrast for the two contrast agents. A high degree of correlation was noted between the two blinded readers. When post-contrast image sets were compared between contrast agents, there was no significant difference in superiority of one agent over the other for any of the evaluators (P > 0.05). No significant differences for any safety parameter were noted between the two agents. Gadoteridol and gadopentetate dimeglumine are effective and well tolerated for use in contrast-enhanced MRI of the CNS at a dose of 0.1 mmol/kg.     

Safety characteristics of gadobenate dimeglumine: clinical experience from intra- and interindividual comparison studies with gadopentetate dimeglumine

PURPOSE: To evaluate the safety and tolerability of gadobenate dimeglumine (Gd-BOPTA) relative to that of gadopentetate dimeglumine (Gd-DTPA) in patients and volunteers undergoing MRI for various clinical conditions. MATERIALS AND METHODS: A total of 924 subjects were enrolled in 10 clinical trials in which Gd-BOPTA was compared with Gd-DTPA. Of these subjects, 893 were patients with known or suspected disease and 31 were healthy adult volunteers. Of the 893 patients, 174 were pediatric subjects (aged two days to 17 years) referred for MRI of the brain or spine. Safety evaluations included monitoring vital signs, laboratory values, and adverse events (AE). RESULTS: The rate of AE in adults was similar between the two agents (Gd-BOPTA: 51/561, 9.1%; Gd-DTPA: 33/472, 7.0%; P = 0.22). In parallel-group studies in which subjects were randomized to either agent, the rate of AE was 10.9% for Gd-BOPTA and 7.9% for Gd-DTPA (P = 0.21). In the subset of subjects receiving both agents in intraindividual crossover trials, the rate of AE was 8.0% for Gd-BOPTA and 8.5% for Gd-DTPA (P = 0.84). Results of other safety assessments (laboratory tests, vital signs) were similar for the two agents. CONCLUSION: The safety profile of Gd-BOPTA is similar to Gd-DTPA in patients and volunteers. Both compounds are equally well-tolerated in patients with various disease states undergoing MRI.     

Double-blind, efficacy evaluation of gadobenate dimeglumine, a gadolinium chelate with enhanced relaxivity, in malignant lesions of the brain

BACKGROUND AND PURPOSE: The diagnostic efficacy of gadobenate dimeglumine (Gd BOPTA) was compared with that of gadodiamide (Gd DTPA-BMA) in patients with primary malignant tumors or metastases of the brain. METHODS: A subset of patients was evaluated from the 410 enrolled in the United States in phase III central nervous system clinical trials with gadobenate dimeglumine. From these trials, there were 82 patients with intraaxial malignant neoplasms of the brain, the focus of the current study. Patients were randomized to one of three incremental dosing regimens. Imaging with gadodiamide at doses of 0.1 and 0.3 mmol/kg was compared with gadobenate dimeglumine at doses of 0.05 and 0.15 mmol/kg and at doses of 0.1 and 0.2 mmol/kg. The on-site physician, patient, and all off-site reviewers were blinded to the agent injected and the administered dose. Scans were obtained before contrast administration and within 5 minutes after administration of each dose. The two contrast injections in any one patient were separated by 15 minutes. An independent laboratory performed signal intensity measurements. The magnetic resonance (MR) films were evaluated for level of diagnostic information, number of lesions detected, and confidence in MR imaging diagnosis by two independent board-certified neuroradiologists unaffiliated with any study site. RESULTS: The lesion-to-brain signal intensity ratio after a dose of 0.1 mmol/kg gadobenate dimeglumine was higher than that after a dose of 0.1 mmol/kg gadodiamide, with this result statistically significant (P = 0.02). After the second dose of contrast, results were comparable in all three groups. The level of diagnostic information contained on the MR films increased significantly for all three groups from pre- to postcontrast for both the first and second administered doses. In between-group comparisons, the level of diagnostic information was similar after the first contrast dose for all three dosing regimens. This was also true after the second contrast dose. For all three groups, the number of lesions detected increased significantly postdose (whether first or second). Confidence in MR diagnosis increased from predose to postdose for all three groups, with no statistically significant difference between groups. CONCLUSION: Gadobenate dimeglumine, used at slightly lower doses, is comparable to gadodiamide in terms of efficacy in imaging of malignant intraaxial brain lesions. As with other gadolinium chelates, higher doses (0.15 and 0.2 mmol/kg) of gadobenate dimeglumine offer greater diagnostic information.     

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

OBJECTIVE. We evaluated the extent to which hepatic lesion characterization and detection is improved by using gadobenate dimeglumine for enhancement of MR images. MATERIALS AND METHODS. Eighty-six patients were imaged before gadobenate dimeglumine administration, immediately after the 2 mL/sec bolus administration of a 0.05 mmol/kg dose (dynamic imaging), and at 60-120 min after the IV infusion at 10 mL/min of a further 0.05 nmol/kg dose (delayed imaging). The accuracy for lesion characterization was assessed for a total of 107 lesions. Sensitivity for lesion detection was assessed for a total of 149 lesions detected on either intra-operative sonography, iodized oil CT, CT during arterial portography, or follow-up contrast-enhanced CT as the gold standard. RESULTS. The accuracy in differentiating benign from malignant liver lesions increased from 75% and 82% (the findings of two observers) on unenhanced images alone, to 89% and 80% on dynamic images alone (p<0.001, p = 0.8), and to 90.7% when combining the unenhanced and dynamic image sets (p<0.001, p = 0.023). Delayed images did not further improve accuracy (90% and 91%; p = 0.002, p< 0.05). A similar trend was apparent in terms of accuracy for specific diagnosis: values ranged from 49% and 62% on unenhanced images alone, to 76% and 70% on combined unenhanced and dynamic images (p<0.001, p = 0.06), and to 75% and 70% on inclusion of delayed images (p<0.001, p = 0.12). The sensitivity for lesion detection increased from 77% and 81% on unenhanced images alone, to 87% and 85% on combined unenhanced and dynamic images (p = 0.001, p = 0.267), and to 92% and 89% when all images were considered (p<0.001, p = 0.01). CONCLUSION. Contrast-enhanced dynamic MR imaging with gadobenate dimeglumine significantly increases sensitivity and accuracy over unenhanced imaging for the characterization of focal hepatic lesions, and delayed MR imaging contributes to the improved detection of lesions.     

Gadobenate dimeglumine-enhanced liver MR imaging: value of dynamic and delayed imaging for the characterization and detection of focal liver lesions

The aim of this study was to determine the value of delayed-phase imaging (DPI) of gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging for the evaluation of focal hepatic tumors compared with precontrast imaging and early dynamic phase imaging. The MR images were obtained in 48 patients with 98 focal hepatic tumors. Three-dimensional gradient-echo (GRE) imaging obtained before and 30, 60, and 1 h after administration of 0.1 mmol/kg of gadobenate dimeglumine. Each image set was analyzed qualitatively (lesion detection, conspicuity, delineation, and enhancement pattern on DPI) and quantitatively [signal-to-noise ratio (SNR), tumor–liver contrast-to-noise ratio (CNR)]. Improved lesion-to-liver contrast during the dynamic phase imaging was observed compared with precontrast images. The DPI showed a homogeneous enhancement of liver parenchyma and distinctive enhancement features of focal liver lesions: metastases (85%) showed a target shaped enhancement, and hepatocellular carcinomas (HCCs) showed an inhomogeneous (58%) or homogeneous enhancement (21%). The DPI showed better performance for the detection of metastases than other images by increasing lesion delineation (p<0.05). The absolute CNR of metastasis measured from periphery of the tumors on DPI was greater than precontrast and arterial phase imaging (p<0.05). The Gd-BOPTA during both dynamic and delayed phases provides valuable information for the characterization of focal liver lesions, and furthermore, Gd-BOPTA-enhanced DPI contributed to the improved detection of liver metastasis compared to precontrast and early dynamic imaging.     

Nontraumatic focal lesions of the spleen: assessment of imaging and clinical evaluation

Fifty-nine cases of nontraumatic splenic disease were reviewed to evaluate the roles of clinical findings, computed tomography, ultrasound, and radionuclide scanning in diagnosis and management. Patient groups included lymphoma (30 patients), infarct (11 patients), abscess (9 patients), cyst (5 patients), hemangioma (3 patients), and hamartoma (1 patient). In no case were clinical findings alone sufficient to diagnose a splenic lesion. Clinical and laboratory manifestations were nonspecific in all groups. Moreover, no radiologic study reliably diagnosed splenic lymphoma or leukemia. All other focal splenic lesions were consistently diagnosed noninvasively. Cross-sectional imaging was more useful than radioisotope scanning, and often provided adjunctive diagnosis of extrasplenic pathology. The superior detail, spatial resolution, and sensitivity of computed tomography made it the single most valuable diagnostic modality.     

Contrast-enhanced sonography with SonoVue: enhancement patterns of benign focal liver lesions and correlation with dynamic gadobenate dimeglumine-enhanced MRI

OBJECTIVE: Contrast-enhanced real-time low-mechanical-index sonography is a new diagnostic technique for the assessment of macro- and microcirculation. The purpose of our article is to describe contrast-enhancement patterns of different benign focal liver lesions using the second-generation contrast agent SonoVue and to compare these findings with those of gadobenate dimeglumine-enhanced MRI. CONCLUSION: SonoVue-enhanced real-time low-mechanical-index sonography provides specific contrast-enhancement patterns of different benign focal liver lesions, allowing accurate characterization. Findings on SonoVue-enhanced sonography correlate well with those obtained on gadobenate dimeglumine-enhanced MRI.     

The added value of contrast-enhanced ultrasound in patients with colorectal cancer undergoing preoperative evaluation with extensive gadobenate dimeglumine liver MRI

Objectives  

To evaluate the added value of pre- and intraoperative contrast-enhanced ultrasound (transabdominal, or TCEUS and intraoperative, or ICEUS, respectively) in patients with known or highly suspected colorectal cancer liver metastases (CRLM) who have previously undergone extensive gadobenate dimeglumine (Gd-BOPTA) liver MRI.     

Pharmacokinetics and safety of gadobenate dimeglumine (multihance) in subjects with impaired liver function

RATIONALE AND OBJECTIVES: To characterize the pharmacokinetics of gadolinium and to evaluate the safety of gadobenate dimeglumine (Gd-BOPTA) compared with placebo, in subjects with impaired liver function. METHODS: Volunteer adult subjects with hepatic impairment (Child-Pugh classification B or C) received, randomly and in double-blind fashion, either 0.1 mmol/kg gadobenate dimeglumine (n = 11) or placebo (n = 5) by intravenous injection. Blood and urine gadolinium concentrations were determined by ICP-AES and data were analyzed by compartmental and noncompartmental modeling. A full safety evaluation was performed. No magnetic resonance imaging was performed. RESULTS: A bi-exponential model fit the gadolinium blood concentration-time data for 10 of 11 subjects administered Gd-BOPTA. The mean (CV%) distribution and elimination half-lives for these subjects were 0.18 (71.9) and 2.18 (44.2) hours, respectively. Non-parametric analysis of all 11 subjects revealed a mean (CV%) area under the curve [0-inf] of 138 (41.9) microg(Gd).h/mL. Mean (CV%) values for blood clearance, steady-state volume of distribution, and renal clearance were 172 (36.0) mL/minute, 22.9 (16.7) L, and 142 (49.0) mL/minute, respectively. A mean (CV%) of approximately 80% (24.5) of the administered dose was excreted in urine during 60 to 72 hours. No safety concerns were apparent. CONCLUSION: Hepatic impairment did not modify the pharmacokinetics of gadobenate dimeglumine compared with values reported elsewhere for healthy subjects. The contrast agent was well tolerated and safe with an overall incidence of adverse events comparable to that of placebo.     

增强超声对已行钆贝酸二葡甲胺增强肝脏MRI术前评估的结直肠癌病人的附加价值

目的评估术前(经腹超声,简称TCEUS)以及术中增强超声(术中超声,简称ICEUS)对于已确诊或者高度怀疑结直肠癌肝转移(CRLM)并且已行钆贝酸二葡甲胺(Gd-BOPTA)增强肝脏MRI检查的病人的附加价值。方法对15例病人的31处病变进行TCEUS和MRI的对比,而对9例病人     

Detection and characterization of focal hepatic lesions: comparative study of MDCT and gadobenate dimeglumine-enhanced MR imaging

The aim of this study was to compare the diagnostic performance of multidetector row helical CT (MDCT) and gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (in the detection and characterization of focal liver lesions. Two blind reviewers analyzed the MDCT and MR images of a total of 44 malignant and 85 benign lesions in 46 patients independently. Receiver operating characteristic curves were established to analyze the results for each reviewer and modality.     

Evaluation of gadobenate dimeglumine in hepatocellular carcinoma: results from phase II and phase III clinical trials in Japan.

To evaluate the clinical efficacy of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging for hepatocellular carcinoma (HCC), we reviewed the results of clinical phase II and III trials in Japan. Gd-BOPTA was administered at a dose of 0.1 mmol/kg to 139 patients who were suspected to have HCC. Dynamic phase images [breath-hold T1-weighted gradient echo (GRE)], spin-echo (SE) images obtained within 10 minutes of injection, and delayed breath-hold GRE images obtained 40-120 minutes after injection were evaluated. All post-contrast images were compared with T1- and T2-weighted pre-contrast images. The contrast efficacy for the dynamic study was classified as ( ) or (++) in 92.1% (128/139), in 43.1% (59/137) with SE within 10 minutes of injection, and in 43.2% (60/139) with breath-hold GRE at delayed phase. The increase in lesion-liver contrast-to-noise ratio was best at the arterial phase of dynamic breath-hold GRE. Liver signal-to-noise ratio showed a mean 52.3% increase in delayed phase. Additional information at delayed phase compared with images acquired within 10 minutes of injection (including the dynamic study) was classified as ( ) or (++) in 28.1% (39/139). With regard to safety, the overall incidence of adverse reactions was 5.0% (7/141) of the patients who were suspected to have HCC, all of whom recovered within 12 hours without any sequelae. No clinically important changes were observed in the blood and urine laboratory tests. It was concluded that Gd-BOPTA was well tolerated and effective in both dynamic study and delayed static imaging for the diagnosis of HCC.