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.

Seventy-four patients with one to eight proven intraaxial metastatic lesions to the brain received a total gadobenate dimeglumine dose of 0.3 mmol/kg of body weight, administered as three sequential bolus injections of 0.1 mmol/ kg, at 10-minute intervals over a 20-minute period. Quantitative and qualitative assessments of efficacy were performed after each injection and a full evaluation of safety was conducted. Cumulative dosing produced significant (P < 0.01) dose-related increases in lesion-to-brain (L/B) ratio and lesion signal intensity (SI) enhancement. Two independent, blinded assessors noted additional lesions, compared to unenhanced images in 31% and 33%, 49% and 42%, and 50% and 48% of patients after each cumulative dose, respectively. Significantly more lesions were noted after the first injection, compared to unenhanced images (P ‫؍‬ 0.002 and P < 0.001; assessors 1 and 2, respectively), and after a second injection, compared to the first (P < 0.001 and P ‫؍‬ 0.039; assessors 1 and 2, respectively). Neither assessor noted significantly more lesions after the third injection. For patients with just one lesion observed on unenhanced T1-and T2-weighted images, additional lesions were noted by assessors 1 and 2 for 27% and 26%, 48% and 35%, and 42% and 41% of patients, respectively, following each injection. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced magnetic resonance imaging (MRI). For patients with one lesion observed after 0.1 mmol/kg of gadobenate dimeglumine, additional lesions were noted for 24% and 17% of patients Index terms: gadobenate dimeglumine; Gd-BOPTA; MRI; CNS metastases; lesion detection THE CHOICE BETWEEN SURGERY AND TUMOR irradiation for the treatment of metastatic lesions to the central nervous system (CNS) is highly dependent on the number and size of lesions detected, as well as on their location (1). At present, contrast-enhanced magnetic resonance imaging (MRI) with gadolinium-based MR contrast agents is the diagnostic technique of choice for the detection of CNS metastases, offering greater sensitivity and specificity than unenhanced MRI and contrast-enhanced computed tomography (1-6). However, as regards the specific contrast agent to use for MRI of CNS metastases, there appears little to choose between the majority of agents available; traditional agents (i.e., gadopentetate dimeglumine, Schering AG, Berlin, Germany; gadoterate meglumine, Guerbet, Aulnay-sous-Bois, France; gadodiamide, Nycomed-Amersham, Oslo, Norway; and gadoteridol, Bracco Imaging SpA, Milano, Italy), as well as newer agents, such as gadoversetamide (Mallinckrodt, St. Louis, MO) and new formulations of existing agents (e.g., gadovist, Schering AG, Berlin, Germany), all possess similar T1 relaxivities in plasma or protein-containing aqueous solution (between 4.3-5.6 mM -1 second -1 ) (7-9) and may be expected to produce similar signal intensity (SI) enhancement when administered at equal dose. Studies at the recommended and approved standard dose of ...

Seventy-four patients with one to eight proven intraaxial brain metastases received a total cumulative dose of 0.2 mmol/kg bodyweight gadobenate dimeglumine, administered as sequential injections of 0.05, 0.05 and 0.1 m mol/kg over a 20-min period. MR imaging was performed before the first administration (T2- and T1-weighted sequences) and after each injection of contrast agent (T1-weighted sequences only). Quantitative assessment of images revealed significant (P <0.01) dose-related increases in lesion-to-brain (L/B) ratio and percent enhancement of lesion signal intensity. Qualitative assessment by two independent, blinded assessors revealed additional lesions in 22%, 25% and 38% (assessor 1) and 29%, 32% and 34% (assessor 2) of patients after each cumulative dose when compared with combined T1- and T2-weighted pre-contrast images. Significantly more lesions (P < 0.01) were noted by both assessors after the first injection and by one assessor after each subsequent injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted in 12%, 16% and 28% of patients by assessor 1 following each dose and in 24%, 27% and 30% of patients by assessor 2. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced MRI. For patients with one lesion observed after an initial dose of 0.05 mmol/kg, additional lesions were noted by assessors 1 and 2 in 9.1% and 11.8% of patients, respectively, after a cumulative dose of 0.1 mmol/kg and in a further 9.1% and 5.9% of patients, respectively, after a cumulative dose of 0.2 mmol/kg. No safety concerns were apparent.

Pharmacological functional magnetic resonance imaging (phMRI) is a valuable tool for the investigation of pharmacological effects of a drug on pain processing. We hypothesized that the ibuprofen-arginine combination, in line with its characterlstlc analgesic properties, may influence the phMRI response at the central level, as compared to placebo. Ten healthy subjects underwent a double-blind, placebo-controlled, randomized, cross-over phFMRI study with somatosensory painful stimulation of the right median nerve. We measured the blood oxygen level dependent (BOLD) signal variations induced in conditions of pain after oral administration of either ibuprofen-arginine or placebo formulations. Independent component analysis (leA) was used for the analysis of the tMRI data, without assuming a specific hemodynamic response function (HRF), which may be altered by drug administration. Median nerve electrical painful stimulation mainly activated the primary contralateral and the secondary somatosensory cortices, the insula, the supplementary motor area, and the middle frontal gyrus. Placebo and ibuprofen-arginine administration induced activation bilaterally in the premotor cortex, and an overall reduction in the other pain-related areas, which was more prominent in the left hemisphere. A task-related increase of BOLD signal between drug and placebo was observed bilaterally in the primary somatosensory area and the middle frontal gyrus without any changes in subjective pain scores. Overall, our findings show that ibuprofen-arginine, in line with the characteristic analgesic properties of ibuprofen, influences the BOLD response in specific pain-related brain areas with respect to placebo, with a vasoactive effect possibly due to arginine.Pharmacological functional magnetic resonance imaging (phFMRI) is a functional neuroimaging modality that combines the administration of a given dose of a drug with the imaging of brain activity through the blood oxygen level dependent (BOLD) technique. phFMRI permits to investigate in vivo and non-invasively the direct effects of the drug on hemodynamic response according to an on/off paradigm, or the drug-induced modulation on specific functional networks activated by physiologically controlled stimuli (1). Neuronal activation, as a consequence of stimulation, locally

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