A fluorine-labeled methotrexate as a probe for monitoring tumor antifolate pharmacokinetics: Synthesis, in vitro cytotoxicity, and pilot in vivo 19F magnetic resonance spectra

William M. Spees, Guangli Yang, Darren Veach, Maria Belen Rubio, Jason A. Koutcher, William Bornmann

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)933-939
Number of pages7
JournalMolecular Cancer Therapeutics
Volume2
Issue number10
StatePublished - Oct 2003

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