D.-Y. Lu et al.: 446 Keywords Introduction Anti-cancer agents • Bisdioxopiperazine compounds • Cancer chemotherapy • Probimane • Drug distribution There have been two most difficult problems in cancer biology and therapeutics, neoplasm metastasis and multi-drug-resistances (MDR). Among these two thorny problems, treatments of neoplasm metastasis are especially difficult and should be placed on higher agenda of the highest for its fatalist pathogenesis features and unpredictability of therapeutic outcome at the stage of drug initiation. Also, metastasized tumors often concomitantly manifest the characters of MDR. The treatment investigation of neoplasm metastases is one of the important topics for therapeutic researchers [1–3]. Bisdioxopiperazine compounds (Biz), including ICRF-154, Razoxane (ICRF-159, Raz), ICRF-186 and ICRF-187 (two stereo-isomers of Raz) and ICRF-193, developed in the UK, have been a series of serendipitous agents found to be effective against a model of spontaneous metastasis (Lewis lung carcinoma, 3LL) [4, 5]. Since Biz compounds are unique and conservative in pharmacological actions, their new analog Probimane [4,4'-(propane-1,2-diyl)bis[1-(morpholin-4-ylmethyl)piperazine-2,6-dione; AT-2153, Pro] [6–9] was synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Since previous data showed that Pro has good antiproliferative effects in vitro [8] and moderate anticancer activity against the growth Lewis lung carcinoma in vivo [7], further work to specialized determinations of these characters is imperative and helpful to us. The researches of anti-metastatic drugs, though at the odds nowadays facing, will be the hottest spot and discipline in the future. This work should carefully study the fate of 14C-probimane to help our understanding and knowledge about metastasis treatments of Biz compounds from drug distributions between normal organs, tumor tissues and metastatic foci. O N O14 C N14 C O N O 14 C N 14 N C O N O 4,4'-(propane-1,2-diyl)bis[1-(morpholin-4-ylmethyl)(2,6-14C2)piperazine-2,6-dione] Fig. 1. The structural formulae of 14C-Probimane Materials and methods Drugs and Reagents: 14C-Pro (Specific activity 130kBq.mg-1) (Figure1) were prepared by Prof. Xin Zhang at the Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Science and suspended in normal saline before use. Sci Pharm. 2010; 78: 445–450.