Alberto Spinazzi

Deutsches Krebsforschungszentrum, Heidelburg, Baden-Württemberg, Germany

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Publications (57)186.67 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Multidose presentations of U.S. Food and Drug Administration (FDA)-approved radiographic contrast agents have been considered pharmacy bulk packages. However, the use of pharmacy bulk packages for multipatient dosing does not meet the U.S. Pharmacopeia definition of a pharmacy bulk package. The purpose of this study was to validate and gain FDA approval for a new multidose preparation of iopamidol for safe, compliant multipatient dosing in the CT suite. Materials and methods: An FDA-approved development program was undertaken to determine whether multidose presentations of iopamidol used in combination with a transfer set remain free of chemical and microbiologic contamination during the labeled maximum hold time after container closure penetration and simulated worst-case handling conditions. The program comprised antimicrobial effectiveness testing of iopamidol-300 and iopamidol-370 containers with seven microbes. Microbial growth was evaluated at five time points up to 28 days after introduction. Microbial ingress testing involved inoculation of four challenge sites with each of four microorganisms for up to 14 hours. Chemical compatibility and extractable testing was performed to ensure chemical integrity. Results: No growth of microorganisms occurred. All evaluated samples remained sterile, indicating no microbial contamination through 14 hours of simulated clinical use. No effect on chemical integrity was found in any of the drawn iopamidol samples meeting the chemical specifications for iopamidol, and no leachable compounds were detected. Conclusion: The absence of any chemical or microbiologic contamination led the FDA to approve the iopamidol multidose container and transfer set as a combination product for multipatient use. The approval resulted in a new U.S. Pharmacopeia category of multidose presentation-the imaging bulk package.
    American Journal of Roentgenology 09/2015; 205(4):697-702. DOI:10.2214/AJR.14.14162 · 2.73 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD) and moderate-to-severe impairment of kidney function who had not previously been exposed to gadolinium-based contrast agents (GBCAs) or referred to undergo contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol. Two multicenter prospective cohort studies evaluated the incidence of unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration rate [eGFR] in cohort 1, 30-59 mL/min/1.73 m(2)) or stage 4 or 5 CKD (eGFR in cohort 2, < 30 mL/min/1.73 m(2)) after injection of gadobenate dimeglumine (study A) or gadoteridol (study B). A third study (study C) determined the incidence of NSF in patients with stage 4 or 5 CKD who had not received a GBCA in the 10 years before enrollment. Monitoring for signs and symptoms suggestive of NSF was performed via telephone at 1, 3, 6, and 18 months, with clinic visits occurring at 1 and 2 years. For studies A and B, the populations evaluated for NSF comprised 363 and 171 patients, respectively, with 318 and 159 patients in cohort 1 of each study, respectively, and with 45 and 12 patients in cohort 2, respectively. No signs or symptoms of NSF were reported or detected during the 2 years of patient monitoring. Likewise, no cases of NSF were reported for any of the 405 subjects enrolled in study C. To our knowledge, and consistent with reports in the literature, no association of gadobenate dimeglumine or gadoteridol with unconfounded cases of NSF has yet been established. Study data confirm that both gadoteridol and gadobenate dimeglumine properly belong to the class of GBCAs considered to be associated with the lowest risk of NSF.
    American Journal of Roentgenology 09/2015; 205(3):469-478. DOI:10.2214/AJR.14.14268 · 2.73 Impact Factor
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    ABSTRACT: Gadobenate dimeglumine (MultiHance) has higher r1 relaxivity than gadoterate meglumine (Dotarem) which may permit the use of lower doses for MR imaging applications. Our aim was to compare 0.1- and 0.05-mmol/kg body weight gadobenate with 0.1-mmol/kg body weight gadoterate for MR imaging assessment of brain tumors. We performed crossover, intraindividual comparison of 0.1-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 1) and 0.05-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 2). Adult patients with suspected or known brain tumors were randomized to Arm 1 (70 patients) or Arm 2 (107 patients) and underwent 2 identical examinations at 1.5T. The agents were injected in randomized-sequence order, and the 2 examinations were separated by 2-14 days. MR imaging scanners, imaging sequences (T1-weighted spin-echo and T1-weighted high-resolution gradient-echo), and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images for diagnostic information (degree of definition of lesion extent, lesion border delineation, visualization of lesion internal morphology, contrast enhancement) and quantitatively for percentage lesion enhancement and lesion-to-background ratio. Safety assessments were performed. In Arm 1, a highly significant superiority (P < .002) of 0.1-mmol/kg gadobenate was demonstrated by all readers for all end points. In Arm 2, no significant differences (P > .1) were observed for any reader and any end point, with the exception of percentage enhancement for reader 2 (P < .05) in favor of 0.05-mmol/kg gadobenate. Study agent-related adverse events were reported by 2/169 (1.2%) patients after gadobenate and by 5/175 (2.9%) patients after gadoterate. Significantly superior morphologic information and contrast enhancement are demonstrated on brain MR imaging with 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate. No meaningful differences were recorded between 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate. © 2015 American Society of Neuroradiology.
    American Journal of Neuroradiology 07/2015; 36(9). DOI:10.3174/ajnr.A4468 · 3.59 Impact Factor
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    ABSTRACT: Dedicated contrast agents are now available for contrast-enhanced magnetic resonance angiography (CE-MRA). This study retrospectively compares the safety and diagnostic performance data from Phase III regulatory trials performed to evaluate gadobenate dimeglumine (MultiHance(®)) and gadofosveset trisodium (Vasovist®)) for renal and peripheral CE-MRA. Similar examination and blinded assessment methodology was utilized in all studies to determine the safety and diagnostic performance of the agents for detection of significant (>50%) steno-occlusive disease. Digital Subtraction Angiography (DSA) was used as the standard of truth. Diagnostic performance data (sensitivity, specificity, predictive values [PVs], and likelihood ratios [LRs]) were compared (Chi-square test). CE-MRA with gadobenate dimeglumine was more specific (92.4% vs. 80.5%, p < 0.0001) and accurate (83.6% vs. 77.1%, p = 0.022) than CE-MRA with gadofosveset in the detection of significant renal artery stenosis. The average sensitivity was higher for gadofosveset (74.4% vs. 67.3%, p = 0.011) in peripheral vessels although gadobenate dimeglumine was more specific (93.0% vs. 88.2%, p < 0.0001) with no difference in accuracy (86.6% vs. 86.3%, p = 0.66). PPVs were higher (p < 0.0001) for gadobenate dimeglumine in both vascular territories. Pre- to post-test shifts in the probability of detecting significant disease were greater after gadobenate dimeglumine. Adverse events in the renal and peripheral studies were reported by 9.2% and 7.7% of patients after gadobenate dimeglumine compared with 30.3% and 22.1% of patients after gadofosveset. The diagnostic performance of CE-MRA for the detection of significant steno-occlusive disease is similar with gadofosveset and gadobenate dimeglumine although the rate of adverse events appears higher with gadofosveset.
    European journal of radiology 09/2009; 77(2):358-68. DOI:10.1016/j.ejrad.2009.07.020 · 2.37 Impact Factor
  • Alberto Spinazzi · Miles A Kirchin · Gianpaolo Pirovano
    Journal of Magnetic Resonance Imaging 05/2009; 29(5):1240; author reply 1241. DOI:10.1002/jmri.21741 · 3.21 Impact Factor
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    ABSTRACT: Retrospective analysis of the occurrence of adverse events and the diagnostic efficacy of a paramagnetic contrast agent with weak intermittent protein binding and high relaxivity. Postmarketing surveillance studies for gadobenate dimeglumine (MultiHance, BRACCO Altana Pharma, Constance) were conducted in Germany between 1998 and 2006 and then retrospectively analyzed. Demographic data, relevant comorbidities, and allergies were recorded. The safety and tolerability of MultiHance were logged on a standardized data sheet. A total of 38,568 patients were included in the study. 829 patients (2.1%) had a known intolerance against contrast media. The examined regions included the central nervous system, the liver, and the vascular bed. The injection rate with automated injectors (n = 10456) varied between 1.0 und 3.0 ml/sec in 86.5% of patients. Adverse events totaled 1.2%. 11 patients (0.03%) experienced serious adverse events. The most frequent findings were nausea, vomiting and a feeling of warmth. MultiHance is a safe and very well tolerated contrast agent for magnetic resonance imaging (MRI) with a profile and frequency of adverse events similar to other extracellular MR contrast materials.
    RöFo - Fortschritte auf dem Gebiet der R 04/2009; 181(7):652-7. DOI:10.1055/s-0028-1109202 · 1.40 Impact Factor
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    Frank G Shellock · Alberto Spinazzi
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    ABSTRACT: OBJECTIVE: This article is the first part of a two-part series on MRI safety. In this article, part 1, the topic of MRI contrast agents and nephrogenic systemic fibrosis (NSF) is addressed. CONCLUSION: To prevent incidents and accidents associated with MRI, it is necessary to regularly revisit the safety topics that directly impact patient management especially with respect to the subjects that are "new" (e.g., MRI contrast agents and NSF), those that should be reassessed because of recent changes, topics that deserve emphasis because of controversy or confusion, and information that should be considered in light of new findings.
    American Journal of Roentgenology 11/2008; 191(4):1129-39. DOI:10.2214/AJR.08.1038.1 · 2.73 Impact Factor
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    Frank G Shellock · Alberto Spinazzi
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    ABSTRACT: OBJECTIVE: This article is the second part of a two-part series on MRI safety. In this article, part 2, the topic of screening patients for MRI procedures is addressed. CONCLUSION: To prevent incidents and accidents associated with MRI, it is necessary to regularly revisit the safety topics that directly impact patient management especially with respect to the subjects that are "new," those that should be reassessed because of recent changes, topics that deserve emphasis because of controversy or confusion, and information that should be considered in light of new findings.
    American Journal of Roentgenology 11/2008; 191(4):1140-9. DOI:10.2214/AJR.08.1038.2 · 2.73 Impact Factor
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    ABSTRACT: To determine the diagnostic performance of contrast-enhanced MR angiography (CE-MRA) with four doses of gadobenate dimeglumine for detection of significant steno-occlusive disease of the carotid, renal, and pelvic vasculature. Eighty-four patients with suspected disease of the renal (n = 16), pelvic (n = 41), or carotid (n = 27) arteries underwent CE-MRA (3D-spoiled gradient-echo sequences) at 1.5T. CE-MRA was performed with gadobenate dimeglumine at 0.025, 0.05, 0.1, or 0.2 mmol/kg (23, 24, 19, and 18 patients, respectively) administered at 2 mL/sec. Accuracy, sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) for detection of significant disease (>50% stenosis or occlusion for renal/pelvic arteries; >70% stenosis or occlusion for carotid arteries) was determined by three fully blinded, independent radiologists using conventional digital subtraction angiography (DSA) as reference standard. All comparisons were tested statistically (ANOVA, chi-square, and Mantel-Haenszel tests as appropriate) and reader agreement (kappa) was assessed. Values for accuracy, sensitivity, specificity, PPV, and NPV on CE-MRA were consistently higher for 0.1 mmol/kg gadobenate dimeglumine (accuracy = 95.2-97.3%, sensitivity = 84.2% (all readers), specificity = 96.9-99.2%, PPV = 80.0-94.1%, NPV = 97.6-97.7%). The greater accuracy of the 0.1 mmol/kg dose was significant (P < 0.01, all readers) compared to all other dose groups. Agreement between the three readers was good for all dose groups (kappa >/=0.58), with the highest percent agreement (85.7%) noted for the 0.1 mmol/kg dose. Significantly better diagnostic performance on CE-MRA of the renal, pelvic, and carotid arteries is achieved with a gadobenate dimeglumine dose of 0.1 mmol/kg bodyweight.
    Journal of Magnetic Resonance Imaging 10/2007; 26(4):1020-32. DOI:10.1002/jmri.21127 · 3.21 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    Journal of Magnetic Resonance Imaging 12/2006; 24(6):1378-85. DOI:10.1002/jmri.20764 · 3.21 Impact Factor
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    ABSTRACT: Prospective studies and retrospective analyses were undertaken to evaluate the clinical safety of gadobenate dimeglumine (MultiHance) and to assess tolerability in special populations. A total of 3092 subjects received MultiHance in 79 clinical trials. Data from comparisons with other contrast agents and studies in children, subjects with hepatic or renal impairment, or subjects with coronary artery disease were reviewed. Postmarketing safety surveillance data after more than 1.5 million applications were also evaluated. In total, 413 of 2982 (14%) adult subjects receiving MultiHance reported at least one adverse event (AE) definitely or potentially related to MultiHance, an incidence that was similar to that observed with placebo (21/127, 17%) or active controls (59/723, 8%). In crossover studies, 23 of 287 (8%) subjects receiving MultiHance experienced AE compared with 25 of 295 (9%) receiving gadopentetate dimeglumine (Magnevist). No increased AE rate was observed in children and no worsening of renal or liver function was observed in subjects with hepatic or renal impairment. No detrimental effect on cardiac electrophysiology could be observed from a retrospective analysis of ECG parameters in more than 1000 patients and healthy volunteers. The AE reporting rate from postmarketing safety surveillance of MultiHance was 0.05%. Serious AEs were rarely reported and included dyspnea, nausea, urticaria, hypotension, and anaphylactoid reactions. MultiHance appears to be well tolerated in adults and children and in subjects with impaired liver or kidney function or coronary artery disease. In controlled trials, MultiHance demonstrated a similar safety profile to that of Magnevist.
    Investigative Radiology 07/2006; 41(6):500-9. DOI:10.1097/01.rli.0000209661.99225.c2 · 4.44 Impact Factor
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    ABSTRACT: Gadobenate dimeglumine (Gd-BOPTA) possesses a two-fold higher T1 relaxivity compared to other available gadolinium contrast agents. The study was conducted to evaluate the benefits of this increased relaxivity for MR imaging of intracranial enhancing brain lesions. Forty-five patients (31 males, 14 females) with suspected glioma or cerebral metastases were evaluated. Patients received Gd-BOPTA and either Gd-DTPA (n = 23) or Gd-DOTA (n = 22) in fully randomized order at 0.1 mmol/kg body weight and at a flow rate of 2 ml/s. The second agent was administered 1-14 days after the first agent. Images were acquired precontrast (T1wSE, T2wFSE sequences) and at sequential postcontrast time-points (T1wSE sequences at 0, 2, 4, 6, and 8 and 15 min and a T1wSE-MT sequence at 12 min) at 1.0 or 1.5 T using a head coil. Determination of contrast enhancement was performed quantitatively (lesion-to-brain ratio, contrast-to-noise ratio, and percent enhancement) and qualitatively (border delineation, internal morphology, contrast enhancement, and diagnostic preference) by two independent, fully blinded readers. Images from 43/45 patients were available for quantitative assessment. After correction for precontrast values, significantly greater lesion-to-brain ratio (P < .003), contrast-to-noise ratio (P < .03), and percent enhancement (P < .0001) was noted by both readers for Gd-BOPTA-enhanced images at all time-points from 2 min postcontrast. Qualitative assessment of all patients similarly revealed significant preference for Gd-BOPTA for lesion border delineation (P < .004), lesion internal morphology (P < .008), contrast enhancement (P < .0001), and diagnostic preference (P < .0005). The greater T1 relaxivity of Gd-BOPTA permits improved visualization of intracranial enhancing lesions compared to conventional gadolinium agents.
    Academic Radiology 06/2006; 13(6):744-51. DOI:10.1016/j.acra.2006.02.056 · 1.75 Impact Factor
  • ECR ’06, Wien, Austria; 03/2006
  • V. Lorusso · G. Pirovano · A. Spinazzi
    Contrast Media & Molecular Imaging 03/2006; 1(2):52-52. DOI:10.1002/cmmi.2 · 2.92 Impact Factor
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    ABSTRACT: The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.
    British Journal of Radiology 02/2006; 79(937):44-51. DOI:10.1259/bjr/23954854 · 2.03 Impact Factor
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    ABSTRACT: Gadobenate dimeglumine (Gd-BOPTA) demonstrates superior enhancement of brain tumours in adult patients than Gd-DTPA. To determine whether Gd-BOPTA has advantages over Gd-DTPA for enhanced MR imaging of paediatric brain and spine tumours. Sixty-three subjects, aged 6 months to 16 years, who were enrolled in a prospective, fully blinded, randomized parallel-group phase III clinical trial, received 0.1 mmol/kg doses of either Gd-BOPTA (n=29) or Gd-DTPA (n=34). The MR images were acquired before and within 10 min of contrast agent injection. The primary objective was to compare the difference from pre-dose to post-dose lesion visualization between Gd-BOPTA and Gd-DTPA. Lesion visualization was determined as the sum of individual scores for three criteria of lesion morphological characteristics (lesion border delineation, internal morphology, and contrast enhancement), each assessed qualitatively using 4-point scales. Quantitative evaluation compared changes in lesion-to-background (LBR) and contrast-to-noise (CNR) ratios and per cent enhancement. Monitoring for adverse events and evaluation of vital signs and laboratory values was performed. Pre-dose to post-dose changes in lesion visualization were significantly better for Gd-BOPTA for both lesion level (2.68+/-2.17 vs. 1.05+/-1.90, P=0.0106) and patient level (2.55+/-2.18 vs. 1.14+/-1.68, P=0.0079) comparisons. The mean pre-dose to post-dose change in CNR was greater for Gd-BOPTA (9.13+/-15.36) than Gd-DTPA (2.18+/-9.90), but the difference was only marginally significant (P=0.0779; 95% CI: -0.553, 14.454) because of wide variations of signal intensity between lesions. Similar findings were obtained for LBR and per cent enhancement. No differences between the agents were noted in terms of safety parameters. At an equivalent dose Gd-BOPTA is significantly better than Gd-DTPA for visualization of enhancing CNS tumours in paediatric patients.
    Pediatric Radiology 06/2005; 35(5):501-10. DOI:10.1007/s00247-004-1392-4 · 1.57 Impact Factor
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    ABSTRACT: To prospectively and intraindividually compare 0.1 mmol/kg gadobenate dimeglumine with 0.2 mmol/kg gadopentetate dimeglumine for contrast material-enhanced magnetic resonance (MR) angiography of the renal arteries. Institutional review board approval was granted by each of three participating centers. The study accorded with international standards for good clinical practice and Declaration of Helsinki and subsequent amendments. Patients gave written informed consent before enrollment. Patients (n = 34) underwent two MR angiographic examinations more than 48 hours but less than 12 days apart. Gadobenate dimeglumine followed by gadopentetate dimeglumine was administered in 18 patients; the order of administration was reversed in 16 patients. A 1.5-T MR imager was used with a phase-encoded three-dimensional spoiled breath-hold pulse sequence. Two blinded independent readers qualitatively assessed randomized subtracted maximum intensity projection images. A three-point scale for diagnostic quality (0, poor; 1a or 1p, moderate; and 2a or 2p, adequate [a and p refer, respectively, to absence and presence of vascular lesions]) was used to score each of nine segments of the abdominal aorta and both renal arteries (possible overall score, 18). Quantitative assessment (vessel signal-to-noise ratio [SNR], vessel-muscle contrast-to-noise ratio [CNR]) of source images was performed for regions of interest in supra-, juxta-, and infrarenal aorta segments and psoas muscle. Data were tested with analysis of variance for two-period crossover design. Interreader agreement was evaluated with Cohen kappa statistics. No difference in mean image quality between the two contrast agents was observed; scores for gadobenate dimeglumine and gadopentetate dimeglumine were 15.15 and 15.23 for reader 1 and 16.77 and 17.01 for reader 2. The order of contrast material administration likewise produced no quality differences: readers 1 and 2 reported scores of 14.4 +/- 4.2 (standard deviation) and 16.7 +/- 2.3, respectively, when gadobenate dimeglumine was given first, and 15.2 +/- 1.8 and 16.6 +/- 1.6, respectively, when gadopentetate dimeglumine was given first. Results of quantitative evaluation showed increasing SNR and CNR with gadobenate dimeglumine in segments at progressively lower levels of the aorta, but increases in SNR and CNR at the infrarenal aorta (48.3 vs 40.6 and 44.2 vs 36.4, respectively) were not significant (P = .05 for both). Gadobenate dimeglumine at a dose of 0.1 mmol/kg is comparable to gadopentetate dimeglumine at 0.2 mmol/kg for contrast-enhanced renal MR angiography.
    Radiology 03/2005; 234(2):399-408. DOI:10.1148/radiol.2342040023 · 6.87 Impact Factor
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    ABSTRACT: To prospectively compare intraindividual effects of 0.2 mmol/kg gadobenate dimeglumine and placebo (saline) on cardiac electrophysiology in healthy volunteers and patients with coronary artery disease (CAD). Gadobenate dimeglumine and saline placebo were injected intravenously approximately 72 hours apart in randomized crossover fashion in 24 healthy volunteers and 23 patients with CAD. Twelve-lead ambulatory (Holter) electrocardiographic (ECG) monitoring was performed from 3 hours preinjection to 24 hours postinjection. Quantitative and qualitative evaluation was performed with automated algorithmic interpretations and blinded assessment by one cardiologist. Possible QT-interval prolongation was evaluated after correction for heart rate on an individualized basis and by means of Bazett formula. Statistical analyses based on two-sided confidence intervals (CIs) were performed by using a linear model for a two-period crossover design. All subjects were monitored for vital signs, laboratory variables, and adverse events. Placebo was administered before contrast agent in 12 volunteers and 12 patients and after contrast agent in 12 volunteers and 11 patients. For mean increase in QTc interval from baseline, a nonsignificant difference of 3.1 msec was noted between gadobenate dimeglumine and placebo (95% CI: -1.8, 8.0) after individualized correction. Overcorrection for heart rate was noted with Bazett formula (mean difference, 5.6 msec; 95% CI: -2.2, 13.5). Cardiologist findings were consistent with automated readings. Similar findings were noted for healthy volunteers and patients with CAD. No differences between treatments were noted for any evaluation, although more frequent qualitative changes were noted in patients with CAD. Adverse events were noted in seven of 47 (15%) subjects after gadobenate dimeglumine injection and in five of 47 (11%) subjects after injection of placebo. Injection of 0.2 mmol/kg gadobenate dimeglumine has no detrimental effect on cardiac electrophysiology or other safety parameters in healthy volunteers or patients with CAD.
    Radiology 12/2004; 233(2):555-65. DOI:10.1148/radiol.2332031802 · 6.87 Impact Factor
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    ABSTRACT: PURPOSE To compare gadobenate dimeglumine (Gd-BOPTA), a contrast agent with high in vivo T1-relaxivity (9.7 mmol�1s�1) with gadopentetate dimeglumine (Gd-DTPA) for enhancement and visualization of central nervous system (CNS) lesions in pediatric patients. METHOD AND MATERIALS A total of 63 pediatric patients with CNS (brain and spine) lesions received 0.1 mmol/kg BW doses of either Gd-BOPTA (n=29; mean age 7.5�4.8 years) or Gd-DTPA (n=34; mean age 7.9�4.7 years). MR images were acquired before (T1+T2wSE) and within 10 minutes (T1wSE) of contrast agent injection. Blinded unpaired and paired qualitative assessment in 26 (Gd-BOPTA) and 32 (Gd-DTPA) patients was performed to compare pre- to post-dose changes in quality of lesion visualization (5-point scales for border delineation, visualization of internal morphology, contrast enhancement). Quantitative evaluation in 19 (Gd-BOPTA) and 23 (Gd-DTPA) patients was performed to compare changes in lesion-to-background ratio (L/B), contrast-to-noise ratio (CNR) and % enhancement (%En). RESULTS Unpaired post-dose scores for lesion border delineation, visualization of internal morphology and contrast enhancement were 3.3�0.6, 3.4�0.6 and 3.4�0.6 for Gd-BOPTA, respectively, and 3.1�0.7, 3.4�0.6 and 3.1�0.7 for Gd-DTPA, respectively. The pre- to post-dose changes were significantly superior for Gd-BOPTA compared to Gd-DTPA for border delineation (p=0.018) and contrast enhancement (p=0.006) and equivalent for visualization of internal morphology (p=0.126). Paired assessments revealed non-significant superiority for Gd-BOPTA for border delineation and visualization of internal morphology and significant superiority for contrast enhancement (p=0.04). Significantly better performance for Gd-BOPTA was noted also for lesion-by-lesion assessments of border delineation and contrast enhancement (p<0.01, all assessments). Mean post-dose values for L/B, CNR and %En were all superior for Gd-BOPTA compared to Gd-DTPA (0.5�0.4 vs. 0.3�0.4; 9.1�15.4 vs. 2.2�9.9; 66.6�47.4 vs. 42.8�39.0, respectively). CONCLUSIONS Gd-BOPTA demonstrates qualitative and quantitative superiority over Gd-DTPA for contrast enhancement of CNS lesions in pediatric patients. DISCLOSURE M.A.K.,A.S.,G.P.,B.H.: These authors are emloyees of Bracco Diagnostics Inc. or Bracco Imaging SpA
    Radiological Society of North America 2004 Scientific Assembly and Annual Meeting; 11/2004
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    ABSTRACT: The purpose of this study was to evaluate the clinical efficacy and dose response relationship of three doses of gadobenate dimeglumine for MRI of the breast and to compare the results with those obtained after a dose of 0.1 mmol/kg of body weight of gadopentetate dimeglumine. SUBJECTS AND METHODS. Gadobenate dimeglumine at 0.05, 0.1, or 0.2 mmol/kg of body weight or gadopentetate dimeglumine at 0.1 mmol/kg of body weight was administered by IV bolus injection to 189 patients with known or suspected breast cancer. Coronal three-dimensional T1-weighted gradient-echo images were acquired before and at 0, 2, 4, 6, and 8 min after the administration of the dose. Images were evaluated for lesion presence, location, size, morphology, enhancement pattern, conspicuity, and type. Lesion signal intensity-time curves were acquired, and lesion matching with on-site final diagnosis was performed. A determination of global lesion detection from unenhanced to contrast-enhanced and combined images was performed, and evaluations were made of the diagnostic accuracy for lesion detection and characterization. A full safety evaluation was conducted. Significant dose-related increases in global lesion detection were noted for patients who received gadobenate dimeglumine (p < 0.04, all evaluations). The sensitivity for detection was comparable for 0.1 and 0.2 mmol/kg of gadobenate dimeglumine, and specificity was highest with the 0.1 mmol/kg dose. Higher detection scores and higher sensitivity values for lesion characterization were found for 0.1 mmol/kg of gadobenate dimeglumine compared with 0.1 mmol/kg of gadopentetate dimeglumine, although more variable specificity values were obtained. No differences in safety were observed, and no serious adverse events were reported. Gadobenate dimeglumine is a capable diagnostic agent for MRI of the breast. Although preliminary, our results suggest that 0.1 mmol/kg of gadobenate dimeglumine may offer advantages over doses of 0.05 and 0.2 mmol/kg of gadobenate dimeglumine and 0.1 mmol/kg of gadopentetate dimeglumine for breast lesion detection and characterization.
    American Journal of Roentgenology 09/2003; 181(3):663-76. DOI:10.2214/ajr.181.3.1810663 · 2.73 Impact Factor

Publication Stats

2k Citations
186.67 Total Impact Points


  • 2006
    • Deutsches Krebsforschungszentrum
      • Division of Radiology
      Heidelburg, Baden-Württemberg, Germany
    • Bracco Group
      Milano, Lombardy, Italy
  • 2001
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
    • Daito Bunka University
  • 1999
    • Hospital San Juan De La Cruz
      Úbeda, Andalusia, Spain
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany