Tumor selective enhancement of radioactivity uptake in mice treated with alpha-difluoromethylornithine prior to administration of 14C-putrescine

Abstract

A group of EMT6 tumor bearing male BALB/c mice which had been treated with alpha-difluoromethylornithine (DFMO, a specific, irreversible inhibitor of ornithine decarboxylase, the enzyme which catalyzes the biosynthesis of putrescine), 8 mg/mouse, ip, 20 and 5 hrs before the 14C-putrescine dose, and a group of control animals were administered 14C-putrescine (0.5 muCi, 0.1 mCi/mmol, iv) 60 min prior to sacrifice. Radioactivity uptake data was obtained for the tumor and 13 major normal organs. In the control animals the tumor exhibited one of the highest uptakes of radioactivity. For DFMO-pretreated mice the radioactivity distribution among most of the normal tissues was not very different from that obtained for the control animals. However, the uptake into the tumor was enhanced by a factor of approximately 4. So, high tumor-to-tissue ratios (3.8, lung to 38, brain) were attained as a result of DFMO treatment.