Bousquet J C, Saini S, Stark D D, Hahn P F, Nigam M, Wittenberg J, Ferrucci J T
Department of Radiology, Massachusetts General Hospital, Boston 02114.
Radiology. 1988 Mar;166(3):693-8. doi: 10.1148/radiology.166.3.3340763.
The relaxivity, biodistribution, and toxicity of the gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) complex were evaluated. This cyclic complex has much greater in vitro stability (10(28)) than similar noncyclic complexes such as gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) (10(23)) or gadolinium-ethylenediaminetetraacetic acid (Gd-EDTA) (10(17)). The T1 relaxivity of Gd-DOTA (meglumine salt) determined in saline and in liver tissue at 20 MHz was similar to the relaxivity of Gd-DTPA. Tissue proton relaxation enhancement (PRE) correlated closely with chemical measurement of tissue gadolinium concentration. In rats, the biodistribution of Gd-DOTA was similar to Gd-DTPA with a distribution half-life of 3 minutes and an elimination half-life of 18 minutes. The median lethal dose (LD50) in mice of Gd-DOTA was 93% higher than that of Gd-DTPA; the calculated safety factor (ratio of LD50 to effective dose) was 53 for Gd-DOTA and 28 for Gd-DTPA. The data suggest that in vitro stability correlates with in vivo safety.
对钆-四氮杂环十二烷四乙酸（Gd-DOTA）复合物的弛豫率、生物分布及毒性进行了评估。这种环状复合物在体外的稳定性（10²⁸）比类似的非环状复合物如钆-二乙烯三胺五乙酸（Gd-DTPA）（10²³）或钆-乙二胺四乙酸（Gd-EDTA）（10¹⁷）要高得多。在20兆赫时，在生理盐水和肝组织中测定的Gd-DOTA（葡甲胺盐）的T1弛豫率与Gd-DTPA的弛豫率相似。组织质子弛豫增强（PRE）与组织钆浓度的化学测量密切相关。在大鼠中，Gd-DOTA的生物分布与Gd-DTPA相似，分布半衰期为3分钟，消除半衰期为18分钟。Gd-DOTA在小鼠中的半数致死剂量（LD50）比Gd-DTPA高93%；计算得出的安全系数（LD50与有效剂量之比）Gd-DOTA为53，Gd-DTPA为28。数据表明体外稳定性与体内安全性相关。
