Pre-clinical evaluation of gadobutrol: A new, neutral, extracellular contrast agent for magnetic resonance imaging
Pre-clinical evaluation of gadobutrol: A new, neutral, extracellular contrast agent for magnetic resonance imaging
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DOI：
10.1016/0720-048x(95)00679-k
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发表时间：
1995-11-01
影响因子：
3.3
通讯作者：
Press, WR
中科院分区：
文献类型：
--
作者：
Vogler, H;Platzek, J;Press, WR
10-（2,3-二羟基-1 -羟甲基丙基）- 1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸（gadobutrol）的Gd3+配合物是一种新的中性gd螯合物，可作为核磁共振成像（MRI）的细胞外造影剂。静脉注射后狗血药浓度下降，终末半衰期约为45 min，清除率约为3.75 ml/min /kg，分布体积为0.23,1/kg提示细胞外分布。大鼠体内生物分布实验显示，静脉注射7天后，体内仅残留极少量（0.16%）剂量。只能在肝脏、肾脏和骨骼中检测到可测量的Gd。渗透压（0.5 mol/l时0.57 osmol/kg， 1 mol/l时1.39 osmol/kg）在其他低渗透压MRI造影剂的范围内。组胺释放试验和溶菌酶抑制试验表明，与生物学相关分子的相互作用很小。小鼠体内23 mmol/kg的剂量限（50）加上相对较高的T-1松弛度（0.47 T时为5.6 l/mmol / s， 2 T时为6.1 l/mmol / s），保证了较高的安全性。在初步影像学实验中，gadobutrol对大鼠不同病变（脑梗死、脑肿瘤）均产生高增强。0.1 mmol/kg的典型临床剂量增加三倍，可为这种类型的病变提供额外的诊断增益。
The Gd3+-complex of 10-(2,3-dihydroxy-l-hydroxymethylpropyl)- 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid(gadobutrol) is a new, neutral Gd-chelate for use as an extracellular contrast agent in magnetic resonance imaging (MRI). The blood level in dogs after intravenous (i.v.) injection decreased with a terminal half-life of about 45 min, the clearance was about 3.75 ml/min per kg and the distribution volume of 0.23 If 1/kg suggested an extracellular distribution. Biodistribution experiments in rats revealed that only a very small amount (0.16%) of the dose was left in the body 7 days after i.v. injection. Measurable amounts of Gd could be detected only in the liver, kidneys and bones. The osmolality (0.57 osmol/kg at 0.5 mol/l and 1.39 osmol/kg at 1 mol/l) is in the range of other low osmolality contrast media for MRI. Only very little interaction with biologically relevant molecules was suggested by a histamine release test and a lysozyme inhibition test. An i.v.-LD(50),, of 23 mmol/kg in mice combined with a comparatively high T-1,-relaxivity (5.6 l/mmol per s at 0.47 T and 6.1 l/mmol per s at 2 T) in plasma promises a high margin of safety. In preliminary imaging experiments, gadobutrol caused high enhancement in different lesions (cerebral infarct, brain tumor) of the rat. Tripling of the typical clinical dose of 0.1 mmol/kg was shown to provide additional diagnostic gain in lesions of this type.