Chain-fluorinated polyamines as tumor markers--I. In vivo transformation of 2,2-difluoroputrescine into 6,6-difluorospermidine and 6,6-difluorospermine.
1. Injection of 2,2-difluoroputrescine (DFPut) into the yolk sac of chick embryos causes the formation of 6,6-difluorospermidine (6,6DFSpd) and 6,6-difluorospermine (6,6DFSpm), demonstrating that the difluoroanalogs of putrescine and spermidine are in vivo substrates of spermidine and spermine synthase, respectively. 2. Depletion of tissue putrescine and spermidine concentrations by administration of D,L-alpha-difluoromethylornithine (DFMO, Ornidyl) causes a very marked enhancement of difluoropolyamine formation from DFPut. 3. The major accumulation of 6,6DFSpd and 6,6DFSpm in DFMO-pretreated rodents occurs in small intestines and tumors, i.e. in tissues with high cell proliferation rates, which are also the most susceptible to polyamine depletion by inhibition of ornithine decarboxylase. 4. Their preferential accumulation in tumors and the fact that DFPut and its metabolites seem not to exert toxic effects, suggest DFPut as a serious candidate for the use as probe in 19F-NMR imaging of tissues with a high proliferation rate and a high rate of polyamine biosynthesis.
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001711:Biotransformation; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000032:analysis; D008175:Lung Neoplasms / Q000032:analysis; D051379:Mice; D011073:Polyamines / Q000032:analysis*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011915:Rats, Inbred BUF; D013095:Spermidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D014408:Biomarkers, Tumor; D011073:Polyamines; C054485:6,6-difluorospermidine; C054486:6,6-difluorospermine; C054484:2,2-difluoroputrescine; D013096:Spermine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine