The synthesis and characterization of 3′-fluoromethotrexate (FMTX), a novel fluorine-labeled analogue of methotrexate, are presented. Molecular modeling studies indicate that the fluorine atom causes only minimal changes in the structure/binding in the complex of the antifolate with thymidine synthetase and dihydrofolate reductase (DHFR). The in vitro cytotoxicity of this compound is shown to be equivalent to that of the parent antifolate compound. While the focus of this report is the synthetic technique of FMTX, it is also demonstrated that tumor accumulation of the labeled compound in vivo can be observed via 19F magnetic resonance spectroscopy (MRS) in a human tumor xenograft model.
|Number of pages||7|
|Journal||Molecular Cancer Therapeutics|
|State||Published - Oct 2003|