A fluorine-labeled methotrexate as a probe for monitoring tumor antifolate pharmacokinetics: Synthesis, in vitro cytotoxicity, and pilot in vivo (19)F magnetic resonance spectra Journal Article
| Authors: | Spees, W. M.; Yang, G.; Veach, D.; Rubio, M. B.; Koutcher, J. A.; Bornmann, W. |
| Article Title: | A fluorine-labeled methotrexate as a probe for monitoring tumor antifolate pharmacokinetics: Synthesis, in vitro cytotoxicity, and pilot in vivo (19)F magnetic resonance spectra |
| 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. © 2003 American Association for Cancer Research. |
| Keywords: | dose response; methotrexate; methodology; protein conformation; mouse; animal; metabolism; animals; mice; antimetabolites, antineoplastic; dose-response relationship, drug; cell line, tumor; time; time factors; chemistry; tumor cell line; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; models, molecular; chemical structure; neoplasm transplantation; dihydrofolate reductase; ic 50; inhibitory concentration 50; tetrahydrofolate dehydrogenase; antineoplastic antimetabolite; models, chemical; synthesis; thymidine; cancer transplantation; fluorine radioisotopes; fluorine; chemical model; humans; human; article |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 2 |
| Issue: | 10 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2003-10-01 |
| Start Page: | 933 |
| End Page: | 939 |
| Language: | English |
| PUBMED: | 14578458 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
