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Chain‐Fluorinated polyamines as tumour markers. iii. determination of geminal difluoropolyamines and their precursor 2,2‐difluoroputrescine in normal tissues and experimental tumours by in vitro and in vivo 19 f NMR spectroscopy
Author(s) -
Hull W. E.,
Kunz W.,
Port R. E.,
Seiler N.
Publication year - 1988
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1940010104
Subject(s) - spermidine , spermine , polyamine , in vivo , chemistry , in vitro , biochemistry , polyamine oxidase , metabolism , nuclear magnetic resonance spectroscopy , stereochemistry , enzyme , biology , microbiology and biotechnology
Treatment of laboratory animals bearing transplantable tumours with α‐difluoromethylornithine, an inhibitor of ornithine decarboxylase, followed by 2,2‐difluoroputrescine allows the partial replacement of the endogenous polyamines spermidine and spermine by their fluorine‐containing analogs 6,6‐difluorospermidine and 6,6‐difluorospermine. Quantitative determination of the chain‐fluorinated polyamines in excised tumor tissue by in vitro 19 F NMR spectroscopy at 11.7 T gave results similar to those obtained by extraction and HPLC analysis. The NMR methods allowed the observation of several as yet unidentified geminal difluoropolyamine metabolites with a detection threshold as low as 1 nmole/g. Using a surface coil at 2.4 T, it was possible to detect in 10–20 min fluorinated polyamines in tumour, liver and bladder (urine) of mice in vivo at concentrations of the order of 50–100 nmol/g, i.e., when 2–5% of the natural polyamines have been replaced by their fluoro analogs. Since 6,6‐difluorospermidine and 6,6‐difluorospermine preferentially accumulate in tumours and specific tissues with enhanced polyamine metabolism, it is expected that these compounds may serve as probes for the application of 19 F NMR methods for tumour diagnosis and therapy control. Since significant quantities of additional fluorine‐containing polyamine metabolites were detected in some tissues, 19 F NMR spectroscopy will contribute to our knowledge of polyamine metabolism in normal and tumour tissue.