The biodistribution of an N2N2′ tetradentate gold(III) chelate, which is known to be cytotoxic towards a range of human cancer cell lines, was determined by a radiolabelled equivalent of the compound. The 198Au-labelled gold(III) chelate of a bis(pyrrolide-imine) Schiff base ligand with a three-carbon di(azomethine) linkage was successfully synthesised with a high radiochemical yield of 73% and radiochemical purity of >95%. The high energy γ-ray emitted by the 198Au nucleus was used to follow the biodistribution of the compound in vivo in six male Sprague Dawley rats on a gamma camera. The log Po/w value of the natAu analogue, −1.92(2), showed that the compound is hydrophilic and therefore likely to largely remain in the blood pool. This was confirmed by the biodistribution study, which showed 21% of the injected dose (ID) remained in the blood pool 4.5 h after injection. This decreased to 10.8% over a 24-h period. The activity measured in the lungs, 1.48%ID/g, remained relatively constant over a 24-h period suggesting that the complex had accumulated in the lungs in the form of particulates, and could not be cleared by the test subjects. The t½ for the heart and lungs was greater than 24 h. Excretion of the test compound is seemingly via the kidneys, but is slow with approximately 30% of the ID excreted within 24 h.
一种 N2N2′ 四价
金(III)螯合物对多种人类癌细胞株具有细胞毒性,该化合物的放射性标记等效物确定了它的
生物分布。成功合成了双(
吡咯烷-
亚胺)希夫碱
配体与三碳二(偶氮甲基)连接的 198Au 标记
金(III)螯合物,其放射
化学收率高达 73%,放射
化学纯度大于 95%。利用 198Au 原子核发射的高能 γ 射线,在伽马相机上跟踪了该化合物在六只雄性 Sprague Dawley 大鼠体内的
生物分布情况。natAu 类似物的 Po/w 对数值为-1.92(2),表明该化合物具有亲
水性,因此很可能大部分留在血液池中。
生物分布研究证实了这一点,该研究显示,注射 4.5 小时后,21% 的注射剂量(ID)仍留在血池中。在 24 小时内,这一比例下降到 10.8%。在肺部测得的活性为 1.48%ID/g,在 24 小时内保持相对稳定,这表明复合物以微粒形式在肺部积聚,无法被受试者清除。心脏和肺部的 t½ 大于 24 小时。试验化合物似乎通过肾脏排泄,但排泄速度较慢,约有 30% 的 ID 在 24 小时内排出体外。