Stability testing of gadoteridol and gadobenate dimeglumine formulations under exposure to high-intensity focused ultrasound

在高强度聚焦超声照射下,对钆特醇和钆贝葡胺制剂进行稳定性测试

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Abstract

OBJECTIVE: Contrast-enhanced MRI could be useful to guide high-intensity focused ultrasound treatment (HIFU), but the effects of HIFU on gadolinium-based agents is not known. Here, we tested in vitro the stability of gadoteridol and gadobenate dimeglumine, two widely used MR contrast agents, after exposure to HIFU at power levels typically applied in the clinical practice. METHODS: 0.5 M (gadoteridol and gadobenate dimeglumine) and diluted formulations (1:10 gadoteridol in saline) were exposed to different HIFU sequences. Unexposed and exposed solutions were characterized by high-performance liquid chromatography in terms of concentration of gadolinium complex, free gadolinium and free ligand. RESULTS: Gadoteridol formulation after treatment showed concentrations of the complex not significantly different from control. Free Gd and/or free ligand concentrations in the order of 0.002/0.004% w/w, were observed occasionally without significant correlation with intensity and duration of exposure to HIFU. Gadobenate dimeglumine formulation after treatment showed complex assay content values, by-products (0.24-0.26%) and free BOPTA levels (0.07%) comparable to control sample within the experimental error. CONCLUSION: In the range of conditions explored, HIFU exposure did not induce significant dissociations of gadoteridol and gadobenate dimeglumine, nor a detectable increase in the concentration of free species. ADVANCES IN KNOWLEDGE: Our study strengthens the hypothesis that gadolinium-based contrast agents are stable during HIFU treatment for body applications (e.g. thermal ablation of uterine fibroids).

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