Synthesis of syn- and anti-1-Amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic Acid (FMACBC), Potential PET Ligands for Tumor Detection
| Autor: | Jonathan McConathy, Nicholas E. Simpson, Eugene Malveaux, Vernon M. Camp, Laurent Martarello, Geoffrey Bowers, Mark M. Goodman, Jeffrey J. Olson, Chiab P. Simpson |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Steric effects Fluorine Radioisotopes Amino Acid Transport System A Stereochemistry Carboxylic acid Carboxylic Acids Gliosarcoma Crystallography X-Ray Ligands Chemical synthesis Cyclobutane chemistry.chemical_compound Drug Discovery Tumor Cells Cultured Animals Tissue Distribution Amino Acids chemistry.chemical_classification Brain Neoplasms Brain Stereoisomerism Rats Inbred F344 Rats Tumor detection chemistry Isotope Labeling Amino Acid Transport System L Molecular Medicine Propionates Radiopharmaceuticals Cyclobutanes Neoplasm Transplantation Tomography Emission-Computed |
| Zdroj: | Journal of Medicinal Chemistry. 45:2250-2259 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm010242p |
| Popis: | syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC, 16 and 17), analogues of anti-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid (FACBC), were prepared to evaluate the contributions of C-3 substitution and configuration on the uptake of these radiolabeled amino acids in a rodent model of brain tumors. Radiofluorinated targets [18F]16 and [18F]17 were prepared by no-carrier-added radiofluorination from their corresponding methanesulfonyl esters 12 and 13, respectively, with decay-corrected radiochemical yields of 30% for [18F]16 and 20% for [18F]17. In amino acid transport assays performed in vitro using 9L gliosarcoma cells, both [18F]16 and [18F]17 were substrates for L type amino acid transport, while [18F]17 but not [18F]16 was a substrate for A type transport. Biodistribution studies in normal Fischer rats with [18F]16 and [18F]17 showed high uptake of radioactivity (2.0% dose/g) in the pancreas while other tissues studied, including liver, heart, lung, kidney, blood, muscle, and testis, showed relatively low uptake of radioactivity (1.0% dose/g). In rats implanted intracranially with 9L gliosarcoma cells, the retention of radioactivity in tumor tissue was high at 5, 60, and 120 min after intravenous injection of [18F]16 and [18F]17 while the uptake of radioactivity in brain tissue contralateral to the tumor remained low (0.3% dose/g). Ratios of tumor uptake to normal brain uptake for [18F]16 were 7.5:1, 7:1, and 5:1 at 5, 60, and 120 min, respectively, while for [18F]17 the ratios were 7.5:1, 9:1, and 9:1 at the same time points. This work demonstrates that like anti-[18F]FACBC, [18F]16 and [18F]17 are excellent candidates for imaging brain tumors. |
| Databáze: | OpenAIRE |
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