A fluorine-labeled methotrexate as a probe for monitoring tumor antifolate pharmacokinetics: synthesis, in vitro cytotoxicity, and pilot in vivo 19F magnetic resonance spectra
| Autor: | William M, Spees, Guangli, Yang, Darren, Veach, Maria Belen, Rubio, Jason A, Koutcher, William, Bornmann |
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| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Antimetabolites Antineoplastic Fluorine Radioisotopes Magnetic Resonance Spectroscopy Time Factors Dose-Response Relationship Drug Protein Conformation Inhibitory Concentration 50 Mice Tetrahydrofolate Dehydrogenase Methotrexate Models Chemical Cell Line Tumor Animals Humans Neoplasm Transplantation Thymidine |
| Zdroj: | Molecular cancer therapeutics. 2(10) |
| ISSN: | 1535-7163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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