Takeshita Keizo, Kinoshita Shota, Okazaki Shoko
Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Chem Pharm Bull (Tokyo). 2012;60(1):31-6. doi: 10.1248/cpb.60.31.
To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.
为了开发一种钆磁共振成像(MRI)造影剂的估算方法,研究了钆化合物浓度对硝酰自由基电子自旋共振(ESR)谱的影响。将4-氧代-2,2,6,6-四甲基哌啶-N-氧基(TEMPONE)或4-羟基-2,2,6,6-四甲基哌啶-N-氧基(TEMPOL)溶液与钆化合物溶液混合,并记录ESR谱。磁共振成像造影剂钆-二乙烯三胺五乙酸螯合物(Gd-DTPA)浓度的增加,会使硝酰自由基ESR谱的峰-峰线宽增加,同时其信号高度降低。在高达约50 mmol/L的Gd-DTPA浓度范围内,观察到Gd-DTPA浓度与ESR信号线宽之间呈线性关系,相关系数较高。从直线斜率评估,TEMPONE的响应比TEMPOL高1.4倍。不同钆化合物的响应略有差异;水合钆[N,N-双[2-[(羧甲基)[(甲基氨基甲酰基)甲基]氨基]乙基]甘氨酸根合(3-)](Gd-DTPA-BMA)(6.22 μT·L/mmol)和钆-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸螯合物(Gd-DOTA)(6.62 μT·L/mmol)校准曲线的斜率比Gd-DTPA(5.45 μT·L/mmol)的斜率更陡,而氯化钆(4.94 μT·L/mmol)的斜率比Gd-DTPA的斜率平缓。该方法易于应用。结果表明,如果用每种标准化合物进行校准,该方法可用于粗略估算钆造影剂的浓度。还发现,如果每次取恒定体积的样品溶液并在ESR腔的同一位置进行测量,将信号高度的倒数平方根对造影剂浓度作图可用于估算。