Synthesis and evaluation of novel organogermanium sesquioxides as antitumor agents.
Five new organogermanium sesquioxides have been synthesized and characterized by elemental analysis and IR spectra. All the compounds were tested for antitumor activities against KB, HCT, and Bel cells in vitro. Compound 5 (gamma-thiocarbamido propyl germanium sesquioxide) showed excellent antitumor activity, and its inhibition yield to KB, HCT, and Bel cells was 92.9%, 84.9%, and 70.9%, respectively. A rapid method was described for the labeling compound 5 with (99m)Tc, and the optimum labeling conditions were investigated. The labeling yield is above 90% in pH 7.0, 20 degrees C, reaction time greater than 10 minutes, 1 mg of compound 5, and 0.075 approximately 0.1 mg of SnCl(2). The biodistribution of (99m)Tc labeled compound 5 in nude mice bearing human colonic xenografts was studied. The result showed that the tumor uptakes were 0.73, 0.97, 0.87, and 0.62 ID%/g at 1-hour, 3-hour, 6-hour, and 20-hour postinjection, respectively. T/NT (the uptake ratio for per gram of tumor over normal tissues) was 18.3 for tumor versus brain and 5.81 for tumor versus muscle at 20-hour postinjection. The tumor clearance was slow. The results showed that compound 5 may be developed to be a suitable cancer therapeutic agent.
Zhang
Chun Li
CL
State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100083, China.
Li
Tai Hua
TH
Niu
Shuang Huan
SH
Wang
Rong Fu
RF
Fu
Zhan Li
ZL
Guo
Feng Qin
FQ
Yang
Ming
M