Liu Si-Yen, Chang Chih-Hsien, Lee Te-Wei
Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
Regul Toxicol Pharmacol. 2014 Jul;69(2):217-25. doi: 10.1016/j.yrtph.2014.04.001. Epub 2014 Apr 8.
N,N-Bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA) is used in the preparation of the (188)Re-BMEDA-liposome as a chelator to deliver rhenium 188 into liposomes. Although the safety of the (188)Re-BMEDA-liposome had been established, the use of BMEDA in preparing the liposome is of interest; however, an assessment of its safety is warranted. In this present work, we report on the acute toxicity study of BMEDA in beagles to identify doses causing no adverse effect and doses causing life-threatening toxicity. In a single dose 14-day systemic toxicity study conducted in beagles, BMEDA was without compound-related adverse effects at doses of up to 2mg/kg in a series of clinical observations and clinical pathology examinations. The results of these studies could aid in choosing doses for repeat-dose studies and in the selection of starting doses for Phase 1 human studies.
N,N-双(2-巯基乙基)-N',N'-二乙二胺（BMEDA）在制备(188)Re-BMEDA-脂质体时用作螯合剂，以便将铼188递送至脂质体中。尽管(188)Re-BMEDA-脂质体的安全性已经确立，但BMEDA在脂质体制备中的应用仍值得关注；然而，对其安全性进行评估是必要的。在本研究中，我们报告了BMEDA在比格犬中的急性毒性研究，以确定无不良反应的剂量和导致危及生命毒性的剂量。在对比格犬进行的单次剂量14天全身毒性研究中，在一系列临床观察和临床病理学检查中，剂量高达2mg/kg时BMEDA未出现与化合物相关的不良反应。这些研究结果有助于选择重复剂量研究的剂量以及确定1期人体研究的起始剂量。
