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.     

Low-dose gadobenate dimeglumine versus standard dose gadopentetate dimeglumine for contrast-enhanced magnetic resonance imaging of the liver: an intra-individual crossover comparison

RATIONALE AND OBJECTIVES: Gadobenate dimeglumine (Gd-BOPTA) has a two-fold higher T1 relaxivity compared with gadopentetate dimeglumine (Gd-DTPA) and can be used for both dynamic and delayed liver MRI. This intraindividual, crossover study was conducted to compare 0.05 mmol/kg Gd-BOPTA with 0.1 mmol/kg Gd-DTPA for liver MRI. MATERIALS AND METHODS: Forty-one patients underwent two identical MR examinations separated by >or= 72 hours. Precontrast T1-FLASH-2D and T2-TSE sequences and postcontrast T1-FLASH-2D sequences were acquired during the dynamic and delayed (1-2 hours) phases after each contrast injection. Images were evaluated on-site by two independent, blinded off-site readers in terms of confidence for lesion detection, lesion number, character and diagnosis, enhancement pattern, lesion-to-liver contrast, and benefit of dynamic and delayed scans. Additional on-site evaluation was performed of the overall diagnostic value of each agent. RESULTS: Superior diagnostic confidence was noted by on-site investigators and off-site assessors 1 and 2 for 6, 4 and 2 patients with Gd-BOPTA, and for 3, 1 and 2 patients with Gd-DTPA, respectively. No consistent differences were noted for other parameters on dynamic phase images whereas greater lesion-to-liver contrast was noted for more patients on delayed images after Gd-BOPTA. More correct diagnoses of histologically confirmed lesions (n = 26) were made with the complete Gd-BOPTA image set than with the complete Gd-DTPA set (reader 1: 68% vs. 59%; reader 2: 78% vs. 68%). The overall diagnostic value was considered superior after Gd-BOPTA in seven patients and after Gd-DTPA in one patient. CONCLUSION: The additional diagnostic information on delayed imaging, combined with the possibility to use a lower overall dose to obtain similar diagnostic information on dynamic imaging, offers a distinct clinical advantage for Gd-BOPTA for liver MRI.     

Comparison of gadobenate dimeglumine and gadopentetate dimeglumine: a study of MR imaging and inductively coupled plasma atomic emission spectroscopy in rat brain tumors

BACKGROUND AND PURPOSE: After the advent of extracellular contrast media, hepatobiliary-specific gadolinium chelates were developed to improve the diagnostic value of MR imaging of the liver. Gadobenate dimeglumine (Gd-BOPTA) is a new paramagnetic contrast agent with partial biliary excretion that produces prolonged enhancement of liver parenchyma on T1-weighted images. However, whether Gd-BOPTA is useful as a contrast agent in central nervous system disease, particularly in brain tumors, is unclear. METHODS: The behavior of Gd-BOPTA as a brain tumor-selective contrast agent was compared with that of gadopentetate dimeglumine (Gd-DTPA), an MR contrast agent used in central nervous system disease, in a common dose of 0.1 mmol/kg. An MR imaging study of these two contrast agents was performed, and tissue concentrations were measured with inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: Gd-BOPTA showed better MR imaging enhancement in brain tumors than did Gd-DTPA at every time course until 2 hours after administration and no enhancement in peritumoral tissue and normal brain. Corresponding results with ICP-AES showed significantly greater uptake of Gd-BOPTA in tumor samples than that in peritumoral tissue and normal brain 5 minutes after administration. Gadolinium was retained for a longer time in brain tumors when Gd-BOPTA rather than Gd-DTPA was administered. CONCLUSION: Gd-BOPTA is a useful contrast agent for MR imaging in brain tumors and possibly an effective absorption agent for neutron capture therapy.     

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.     

Low-dose gadobenate dimeglumine versus standard-dose gadopentate dimeglumine for delayed contrast-enhanced cardiac magnetic resonance imaging

RATIONALE AND OBJECTIVES: The purpose of our study was to compare gadopentate dimeglumine (Gd-DTPA) and gadobenate dimeglumine (Gd-BOPTA) for the evaluation of myocardial infarction (MI) and in the grading transmural extent on late-contrast enhanced cardiac magnetic resonance imaging. MATERIALS AND METHODS: Twenty-three patients with clinically proven MI were examined with the use of 0.2 mmol/kg Gd-DTPA and 0.1 mmol/kg Gd-BOPTA in 2 days interval. All patients were examined with the use of segmented two-dimensional inversion-recovery turbo fast-field echo pulse sequence with an inversion time 210-300 milliseconds. Fifteen minutes time delay was used on both examinations after the injection of contrast agent. Contrast-to-noise ratio between normal myocardium and infarcted myocardium and signal intensity ratio (SIR) of the enhanced myocardium to blood pool was derived and compared for each contrast agent. RESULTS: A total of 61 infarcted segments were analyzed. All of the infarcted segments were visualized on both Gd-BOPTA and Gd-DTPA enhanced images. There was statistically no significant difference between 0.2 mmol/kg Gd-DTPA and 0.1 mmol/kg Gd-BOPTA in the mean contrast-to-noise ratio (10.19 versus 10.22; P = .96), SNR (14.29 versus 14.25; P = .96), and SIR (4.34 versus 4.21; P = .38) of the infarcted segments. Intraobserver agreement (kappa) between Gd-DTPA and Gd-BOPTA were R1 = 91% and R2 = 86%. Interobserver agreements between the readers were Gd-DTPA = 85% and Gd-BOPTA = 88%. CONCLUSION: According to our data, the diagnostic efficacy of 0.1 mmol/kg dose Gd-BOPTA is equivalent to that of 0.2 mmol/kg Gd-DTPA for the assessment of MI on delayed enhanced magnetic resonance images.     

Detection of liver metastases: comparison of gadobenate dimeglumine-enhanced and ferumoxides-enhanced MR imaging examinations

PURPOSE: To compare gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance (MR) imaging with ferumoxides-enhanced MR imaging for detection of liver metastases. MATERIALS AND METHODS: Twenty consecutive patients known to have malignancy and suspected of having focal liver lesions at ultrasonography (US) underwent 1.0-T MR imaging with gradient-recalled-echo T1-weighted breath-hold sequences before, immediately after, and 60 minutes after Gd-BOPTA injection. Subsequently, MR imaging was performed with turbo spin-echo short inversion time inversion-recovery T2-weighted sequences before and 60 minutes after ferumoxides administration. All patients subsequently underwent intraoperative US within 15 days, and histopathologic analysis of their resected lesion-containing specimens was performed. Separate qualitative analyses were performed to assess lesion detection with each contrast agent. Quantitative analyses were performed by measuring signal-to-noise and contrast-to-noise ratios (CNRs) on pre- and postcontrast Gd-BOPTA and ferumoxides MR images. Statistical analyses were performed with Wilcoxon signed rank and Monte Carlo tests. RESULTS: Sensitivity of ferumoxides-enhanced MR imaging was superior to that of Gd-BOPTA-enhanced MR imaging for liver metastasis detection (P <.05). Ferumoxides MR images depicted 36 (97%) of 37 metastases detected at intraoperative US, whereas Gd-BOPTA MR images depicted 30 (81%) metastases during delayed phase and 20 (54%) during dynamic phase. All six metastases identified only at ferumoxides-enhanced MR imaging were 5-10 mm in diameter. There was a significant increase in CNR between the lesion and liver before and after ferumoxides administration (from 3.8 to 6.8, P <.001) but not before or after Gd-BOPTA injection (from -4.8 to -5.5, P >.05). CONCLUSION: Ferumoxides-enhanced MR imaging seems to be superior to Gd-BOPTA-enhanced MR imaging for liver metastasis detection. Copyright RSNA, 2002     

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.     

Comparison of Gd-BOPTA with Gd-DTPA in MR imaging of rat liver

A new lipophilic compound, gadolinium benzyloxypropionictetraacetate (BOPTA), with a high rate of biliary excretion was assessed as a magnetic resonance (MR) hepatospecific contrast-enhancing agent and compared with Gd-DTPA (diethylenetriaminepentaacetic acid) in MR imaging of normal rats. T1-weighted spin-echo images obtained before and after administration of each contrast agent at doses of 0.25, 0.5, and 1.0 mmol/kg showed greater enhancement of the liver with Gd-BOPTA than with Gd-DTPA, with the advantage more evident at lower doses. Images obtained with an inversion recovery sequence at the null value of rat liver parenchyma after injection of 0.1- and 0.5-mmol/kg doses of the contrast agent provided better evidence of the greater and longer-lasting hepatic enhancement due to Gd-BOPTA when compared with that of Gd-DTPA. Gd-BOPTA is a potentially good contrast agent for obtaining prolonged enhancement of the liver, permitting studies during the long time needed to acquire conventional T1-weighted images.     

Multishot echo-planar imaging with gadopentetate dimeglumine. Preliminary study of efficacy for detection of hypovascular metastatic liver tumors

OBJECTIVE: To evaluate the usefulness of sequential T2-weighted spin-echo type multishot echo-planar (T2-EP) imaging with gadopentetate dimeglumine for the detection of hypovascular metastatic liver tumors. MATERIAL AND METHODS: Fifteen consecutive patients with 56 proven hypovascular metastatic liver tumors were included in the study. Three observers blindly and independently read the whole-liver images obtained with T2-weighted spin-echo, T2-weighted single-shot fast spin-echo, T1-weighted fast multiplanar spoiled GRASS and T2-EP images obtained before and 25, 60, 90 and 120 s after injection of 0.2 mmol/kg b.w. of gadopentetate dimeglumine. The diagnostic accuracy was estimated by calculating the area under the observer-specific binomial receiver operating characteristics curves (Az). RESULTS: T2-EP images obtained 60 s after contrast injection showed significantly higher contrast-to-noise (C/N) ratios than the other imaging techniques. A combination of all phases of the T2-EP images produced the highest sensitivity and specificity. In terms of the Az value, the diagnostic accuracy for tumor detection achieved with a combination of all phases of the T2-EP images was significantly higher than that with T1-SPGR and T2-SSFSE images (p<0.01). The Az values of the T2-EP images (Az=0.975) were higher than those of T2-CSE images (Az=0.948), but the difference was not significant. CONCLUSION: Our preliminary study revealed that sequential imaging with enhanced T2-EP images was useful for the detection of hypovascular metastatic liver tumors because of its superior C/N ratio and sensitivity.     

Gadobenate dimeglumine--a new contrast agent for MR imaging: preliminary evaluation in healthy volunteers.

Gadobenate dimeglumine (formerly known as Gd-BOPTA) is a recently developed paramagnetic contrast agent that undergoes biliary as well as renal excretion. It may, therefore, be useful in MR imaging of the liver. Its safety, tolerance, and usefulness in visualizing hepatobiliary structures were studied in eight healthy subjects. Axial abdominal images were obtained with T1-weighted spin-echo and gradient-echo sequences at 1.5 T before and after IV administration of gadobenate dimeglumine in doses of 0.005, 0.05, 0.1, and 0.2 mmol/kg body weight. Two subjects received each dose. Administration of 0.1 mmol/kg resulted in a maximum liver enhancement of 149% on the gradient-echo sequence and of 90% on the T1-weighted spin-echo sequence 60 min after injection. The contrast enhancement of the liver remained virtually constant for 2 hr. The signal-to-noise ratio of the biliary tract increased from 38 to 121 after 2 hr on gradient-echo images. In addition, there was significant contrast enhancement of the kidneys. Optimal visualization of the liver parenchyma was achieved with doses of 0.05 and 0.1 mmol gadobenate dimeglumine/kg. Mild to moderate side effects such as nausea and retching, a sense of warmth at the infusion site, and transient pruritus lasting 1 min were reported by three (38%) of the subjects. The initial results of the first application of gadobenate dimeglumine in humans are encouraging because the contrast agent appears to be reasonably well tolerated at the doses appropriate for hepatobiliary imaging. Further clinical studies of this contrast agent are warranted to assess its effect on liver lesion conspicuity and the frequency with which side effects occur.     

Evaluation of the hepatocyte-specific contrast agent gadobenate dimeglumine for MR imaging of acute hepatitis in a rat model

This work was conducted to test the hypothesis that contrast-enhanced MRI with hepatocyte-specific contrast agents facilitates quantitation and mapping of diffuse liver diseases such as hepatitis and cirrhosis. Gadobenate dimeglumine (Gd-BOPTA/Dimeg, Bracco SpA, Milano, Italy) is a new paramagnetic hepatocytespecific contrast agent currently undergoing clinical trials. We have assessed the usefulness of gadobenate dimeglumine for the diagnosis of diffuse liver diseases in a rat model of chemically induced hepatitis. The study was based on the measurements of in vivo liver relaxation times as well as on the acquisition of standard SE images. Acute hepatitis considerably reduced the degree of T1 shortening of liver parenchyma caused by intravenous injection of .25 mmol/kg of gadobenate dimeglumine. Analogously, the enhancement of the MRI signal intensity of the liver of rats with hepatitis observed in T1-weighted spin-echo (SE) images was inferior, in terms of both strength and duration, to that recorded in control rats at doses of .25 mmol/kg and .075 mmol/kg of gadobenate dimeglumine. Our results show that gadobenate dimeglumine enhanced MR imaging has the potential for visualization of hepatitis and for assessment of liver function. Our conclusions differ from those previously published on this subject by other authors. The reasons that led to differing conclusions are discussed.     

Gadobenate dimeglumine (Gd-DTPA) vs gadopentetate dimeglumine (Gd-BOPTA) for contrast-enhanced magnetic resonance angiography (MRA): improvement in intravascular signal intensity and contrast to noise ratio

PURPOSE: The purpose of this study was to compare contrast enhanced MR angiography (MRA) with gadopentetate dimeglumine (Gd-DTPA) to MRA with gadobenate dimeglumine (Gd-BOPTA), a high relaxivity paramagnetic contrast agent. MATERIALS AND METHODS: Twelve patients referred for carotid artery stenosis were examined with MR angiography using a fast spoiled gradient echo sequence. Gd-DTPA and Gd-BOPTA enhanced MR angiography were performed within 48-72 hours using a dose of 0.1 mmol/kg for Gd-BOPTA and 0.2 mmol/kg for Gd-DTPA, at a flow rate of 2 ml/s. Images were evaluated by two blinded radiologists. Qualitative and quantitative evaluations were performed comparing the sets of images from the two examinations. RESULTS: Qualitative evaluation demonstrated superior arterial contrast enhancement and vessel conspicuity with Gd-BOPTA compared with Gd-DTPA. Quantita-tive evaluation showed an improvement in both signal intensity and contrast to noise ratio with Gd-BOPTA. CONCLUSION: The greater relaxivity of Gd-BOPTA, at lower doses, compared with Gd-DTPA, provides higher intravascular signal and signal to noise ratio. Gd-BOPTA appears to be an optimal contrast agent for contrast enhanced MRA.     

The efficacy of gadobenate dimeglumine (Gd-BOPTA) at 3 Tesla in brain magnetic resonance imaging: comparison to 1.5 Tesla and a standard gadolinium chelate using a rat brain tumor model

OBJECTIVES: The objectives of this study were to analyze the differences in contrast enhancement using gadobenate dimeglumine (Gd-BOPTA or MultiHance) at 3 T versus 1.5 T and to compare Gd-BOPTA with a standard gadolinium chelate, gadopentetate dimeglumine (Gd-DTPA or Magnevist), at 3 T in a rat glioma model. MATERIALS AND METHODS: Twelve rats with surgically implanted gliomas were randomized to either comparing Gd-BOPTA at 1.5 T versus 3 T (n=7) or comparing Gd-BOPTA and Gd-DTPA at 3 T (n=5). Matched T1-weighted spin-echo techniques were used for both comparisons and the order of examinations was randomized. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and lesion enhancement (LE) were evaluated using a region-of-interest analysis. A veterinary histopathologist evaluated all brain specimens. RESULTS: In the evaluation of Gd-BOPTA at 3 T and 1.5 T, there were significant increases in SNR, LE, and CNR at 3 T. Average increases in brain and tumor SNR were 93% (P<0.0001) and 92% (P<0.0001), respectively. CNR increased by 121% (P<0.0001). Comparison of Gd-BOPTA and Gd-DTPA at 3 T demonstrated significantly higher CNR and LE with Gd-BOPTA. CNR increased by 35% (P=0.002). LE increased by 44% (P=0.03). CONCLUSIONS: Gd-BOPTA provides significantly higher CNR at 3 T compared with 1.5 T and also demonstrates significantly higher CNR when compared with a standard Gd-chelate at 3 T. As a result of transient protein binding, Gd-BOPTA may be superior to standard gadolinium chelates in neurologic imaging at 3 T.     

A comparative study between Gd-BOPTA, a biliary excretion contrast medium, and Gd-DTPA in the magnetic resonance imaging of the rat liver

A new lipophilic compound, Gd-BOPTA, presenting a high rate (38.6%) of biliary excretion was tested as an hepato-specific MR contrast agent. Its adequacy was compared to that of Gd-DTPA in laboratory animals. T1-weighted spin-echo sequences (TR 220 ms, TE 20 ms) both before and after the administration of the 2 contrast agents (doses: 0.25, 0.5, and 1.0 mmol/kg) showed better liver enhancement with Gd-BOPTA than with Gd-DTPA. Gd-BOPTA superiority was more evident at lower doses, while at 1.0 mmol/kg a comparable enhancement was achieved. Inversion recovery sequence at the T-null of liver parenchyma before contrast (TR 800 ms, TE 30 ms, TI 100 ms) was performed after the injection of 0.1 and 0.5 mmol/kg of Gd-DTPA and Gd-BOPTA. This sequence allowed the good and long-lasting liver enhancement achieved with Gd-BOPTA to be even better demonstrated, while Gd-DTPA provided only a slight and early enhancement with 0.1 mmol/kg and returned to baseline values 60' after the injection of the highest dose (0.5 mmol/kg). Gd-BOPTA proved to be a good contrast agent to obtain prolonged liver enhancement, thus providing the radiologist with the long time needed to acquire conventional T1-weighted pulse sequences.     

Focal nodular hyperplasia: morphologic and functional information from MR imaging with gadobenate dimeglumine.

PURPOSE: To determine whether gadobenate dimeglumine (Gd-BOPTA) is able to provide morphologic and functional information for characterization of focal nodular hyperplasia (FNH). MATERIALS AND METHODS: Sixty-three consecutive patients with proved FNH were retrospectively examined. Magnetic resonance (MR) imaging with T2-weighted turbo spin-echo and T1-weighted gradient-echo sequences was performed. Images were acquired prior to and during the dynamic phase of contrast-material enhancement and 1-3 hours after administration of 0.1 mmol/kg Gd-BOPTA. Qualitative analysis of signal intensity and homogeneity on images in the various phases of the MR study and examination for the presence of central scar or atypical features were performed. On the basis of features observed in the precontrast and dynamic phases, lesions were defined as typical or atypical. Intensity and enhancement patterns of the lesions and scars were also evaluated in the delayed phase. RESULTS: One hundred FNHs were depicted on MR images. Seventy-nine of 100 lesions demonstrated typical morphologic and enhancement characteristics. On delayed phase images, 72% of 100 FNHs appeared hyperintense; 21%, isointense; and 7%, slightly hypointense. The delayed pattern of enhancement was homogeneous, heterogeneous, and peripheral in 58%, 22%, and 20% of 100 FNHs, respectively. Atypical morphologic features and lesion and/or scar enhancement were observed in 21 of 100 FNHs. On delayed phase images, 76% of 100 atypical FNHs appeared hyperintense, 14% isointense, and 10% slightly hypointense. Hyperintensity and isointensity allowed the correct characterization in 90% of atypical FNHs. CONCLUSION: Gd-BOPTA during both dynamic and delayed phases provides morphologic and functional information for the characterization of FNH.     

Delayed MR imaging of hepatocellular carcinoma enhanced by gadobenate dimeglumine (Gd-BOPTA).

The purpose of this study was to determine the efficacy of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance (MR) imaging for evaluation of hepatocellular carcinoma HCC. MR images were obtained in 14 patients with 31 HCC nodules as a part of a phase III clinical trial. T1- and T2-weighted images were obtained before and after iv administration of 0.1 mmol/kg of Gd-BOPTA. Two blinded readers evaluated pre- and delayed postcontrast images separately for detection of tumor nodules. Quantitative measurements of signal-to-noise (SNR) and tumor/liver contrast-to-noise (CNR) ratios were also performed. A signal/intensity ratio was calculated. Tumor enhancement was correlated with histologic findings. Consensus agreement of precontrast T1- and T2-weighted images revealed 23/31 HCC nodules in 14 patients; postcontrast T1-weighted images demonstrated 24/31 HCC nodules in the same number of patients. Combining both pre- and postcontrast images, 27/31 lesions were detected. Four patients had four well-differentiated HCC nodules detected only on postcontrast images, while three well-differentiated lesions in two patients were only seen on precontrast images. Quantitative evaluation showed an SNR ratio increase in both liver parenchyma and HCC nodules, as well as a significant increase in the absolute CNR ratio on postcontrast T1-weighted gradient-recalled images (P < 0.05). Well-differentiated HCC lesions showed a greater enhancement than poorly differentiated HCC lesions.     

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.     

Primary and secondary brain tumors at MR imaging: bicentric intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine

PURPOSE: To evaluate the safety of and compare the enhancement characteristics of gadobenate dimeglumine (MultiHance; Bracco Imaging, Milan, Italy) with those of a standard gadolinium chelate (gadopentetate dimeglumine, Magnevist; Schering, Berlin, Germany) in primary and secondary brain tumors on the basis of qualitative and quantitative parameters, on an intraindiviual basis. MATERIALS AND METHODS: Twenty-seven patients with either high-grade glioma or metastases were enrolled in a bicentric intraindividual crossover study to compare lesion enhancement with doses of 0.1 mmol per kilogram of body weight of 0.5 mol/L gadopentetate dimeglumine and 0.5 mol/L gadobenate dimeglumine. MR imaging was performed before injection (T1-weighted spin-echo [SE] and T2-weighted fast SE acquisitions) and at 1, 3, 5, 7, 9, and 16 minutes after injection (T1-weighted SE acquisitions). Qualitative assessment was performed by blinded off-site readers (for 22 patients) and on-site investigators (for 24 patients) in terms of global contrast enhancement, lesion-to-brain contrast, lesion delineation, internal lesion morphology and structure, tumor vascularization, and global image preference. Additional quantitative assessment with region-of-interest analysis was performed by off-site readers alone. Statistical analysis of qualitative data was performed with the Wilcoxon signed rank test, whereas a nonparametric approach was adopted for analysis of quantitative data. RESULTS: Significant (P <.05) preference for gadobenate dimeglumine over gadopentetate dimeglumine was noted both off-site and on-site for the global assessment of contrast enhancement. For off-site readers 1 and 2 and the on-site investigators, respectively, gadobenate dimeglumine was preferred in 13, 17, and 16 patients; gadopentetate dimeglumine was preferred in four, four, and four patients; and equality was found in five, one, and four patients). Similar preference for gadobenate dimeglumine was noted by off-site readers and on-site investigators for lesion-to-brain contrast and all other qualitative parameters. Off-site quantitative evaluation revealed significantly (P <.05) superior enhancement for gadobenate dimeglumine compared with that for gadopentetate dimeglumine at all time points from 3 minutes after injection. CONCLUSION: Significantly superior contrast enhancement of intraaxial enhancing brain tumors was achieved with 0.1 mmol/kg gadobenate dimeglumine compared with that with 0.1 mmol/kg gadopentetate dimeglumine.     

Contrast-enhanced MR angiography of the run-off vasculature: intraindividual comparison of gadobenate dimeglumine with gadopentetate dimeglumine

PURPOSE: To compare intraindividually gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for multi-station MR Angiography of the run-off vessels. MATERIALS AND METHODS: Twenty-one randomized healthy volunteers received either Gd-BOPTA or Gd-DTPA as a first injection and then the other agent as a second injection after a minimum interval of 6 days. Each agent was administered at a dose of 0.1 mmol/kg bodyweight followed by a 25-mL saline flush at a single constant flow rate of 0.8 mL/second. Images were acquired sequentially at the level of the pelvis, thigh, and calf using a fast three-dimensional (3D) gradient echo sequence. Source, subtracted source, maximum intensity projection (MIP), and subtracted MIP image sets from each examination were evaluated quantitatively and qualitatively on a segmental basis involving nine vascular segments. RESULTS: Significantly (P < 0.05) higher signal-to-noise and contrast-to-noise ratios were noted for Gd-BOPTA compared to Gd-DTPA, with the more pronounced differences evident in the more distal vessels. Qualitative assessmentrevealed no differences in the abdominal vasculature, a preference for Gd-BOPTA in the pelvic vasculature, and markedly better performance for Gd-BOPTA in the femoral and tibial vasculature. Summation of individual diagnostic quality scores for each segment revealed a significantly (P = 0.0001) better performance for Gd-BOPTA compared to Gd-DTPA. CONCLUSION: Greater vascular enhancement of the run-off vasculature is obtained after Gd-BOPTA, particularly in the smaller more distal vessels. Enhancement differences are not merely dose dependent, but may be due to different vascular enhancement characteristics of the agents.     

A comparison of Gd-BOPTA and Gd-DOTA for contrast-enhanced MRI of intracranial tumours

A two-centre intra-individual crossover study was performed in 23 patients with suspected high-grade glioma or metastases to assess and compare the safety and enhancement characteristics of two different MRI contrast media (gadobenate dimeglumine, Gd-BOPTA and gadoterate meglumine, Gd-DOTA) at equivalent doses of 0.1 mmol/kg body weight. T1-weighted spin-echo (SE) and T2-weighted fast SE images were obtained before and T1-weighted images 0, 2, 4, 6, 8 and 15 min after injection. T1-weighted images with magnetisation transfer contrast were acquired 12 min after injection. Qualitative assessment by blinded, off-site readers (reader 1: 19 patients; reader 2: 21) and on-site investigators (23) revealed significant (P 0.005) overall preference for Gd-BOPTA over Gd-DOTA for contrast enhancement (Gd-BOPTA preferred in 18, 15 and 18 cases; Gd-DOTA in 0, 1 and 1 and no preference in 1, 5 and 4; off-site readers 1 and 2, and on-site investigators, respectively). A similar significant preference for Gd-BOPTA was expressed by off-site readers and on-site investigators for lesion-to-brain contrast, lesion delineation, internal lesion structure, and overall image preference. Quantitative assessment by off-site readers revealed significantly (p<0.05) greater lesion enhancement with Gd-BOPTA than with Gd-DOTA at all times from 2 min after injection.