Distribution of radioactivity and anthracycline-fluorescence in tissues of mice one hour after [14C]-labeled AD 32 administration |
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Authors: | Mervyn Israel Abraham M. Karkowsky Vinod K. Khetarpal |
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Affiliation: | (1) Division of Pharmacology, Sidney Farber Cancer Institute, 44 Binney Street, 02115 Boston, MA, USA |
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Abstract: | Summary Levels of radioactivity and total anthracycline fluorescence in tissues of A/JAX mice were compared 1 h after IV administration of unlabeled or [14C]-labeled AD 32 (50 mg/kg). Highest levels of both fluorescence and radioactivity were found in the small intestine (including contents) and liver, a result consistent with the known hepatobiliary excretion of AD 32 and metabolites. Significant accumulations of radioactivity and fluorescence were found in kidney, spleen, large intestine (including contents), lung, and heart. Lesser levels were found in muscle and fat. Little radioactivity and fluorescence were found in brain. Liquid chromatographic analysis of extracts of small intestine and liver homogenates showed N-trifluoroacetyladriamycin (AD 41) as the major fluorescent species, and also revealed N-trifluoroacetyladriamycinol (AD 92) and occasional low levels of AD 32. In addition, there was a major peak of nonfluorescent radioactive material and two fluorescent nonradioactive signals (unknowns 1 and 2), indicative of cleavage of the radiolabel from the chromophore.The abbreviations used are AD 32 N-trifluoroacetyladriamycin-14-valerate - AD 41 N-trifluoroacetyladriamycin - AD 92 N-trifluoroacetyladriamycinol - ADR adriamycin - AD 48 adriamycin-14-valerate - AD 60 13-dihydro-N-trifluoroacetyladriamycin-14-valerate - AMNOL adriamycinol - HPLC high-performance liquid chromatography - TLC thin layer chromatography - SDS sodium dodecylsulfate |
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