Design, Synthesis, and Evaluation of an (18)F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2)
| Autor: | Alison Marshall, Jatinder Kaur, Ole Tietz, Melinda Wuest, Atul Bhardwaj, Frank Wuest, Jenilee Way |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Fluorine Radioisotopes Mice Inbred Strains Biochemistry Mice In vivo Cell Line Tumor Drug Discovery medicine Animals Humans Tissue Distribution General Pharmacology Toxicology and Pharmaceutics Radioactive Tracers IC50 Pharmacology medicine.diagnostic_test biology Cyclooxygenase 2 Inhibitors Molecular Structure Chemistry business.industry Organic Chemistry Radiochemistry Fluorescence Imaging agent In vitro 4-Chloro-7-nitrobenzofurazan Positron emission tomography Celecoxib Cyclooxygenase 2 Drug Design Positron-Emission Tomography biology.protein Molecular Medicine Cyclooxygenase Nuclear medicine business medicine.drug |
| Zdroj: | ChemMedChem. 10(10) |
| ISSN: | 1860-7187 |
| Popis: | A series of novel fluorine-containing cyclooxygenase-2 (COX-2) inhibitors was designed and synthesized based on the previously reported fluorescent COX-2 imaging agent celecoxib-NBD (3; NBD=7-nitrobenzofurazan). In vitro COX-1/COX-2 inhibitory data show that N-(4-fluorobenzyl)-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (5; IC50 =0.36 μM, SI>277) and N-fluoromethyl-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (6; IC50 =0.24 μM, SI>416) are potent and selective COX-2 inhibitors. Compound 5 was selected for radiolabeling with the short-lived positron emitter fluorine-18 ((18) F) and evaluated as a positron emission tomography (PET) imaging agent. Radiotracer [(18) F]5 was analyzed in vitro and in vivo using human colorectal cancer model HCA-7. Although radiotracer uptake into COX-2-expressing HCA-7 cells was high, no evidence for COX-2-specific binding was found. Radiotracer uptake into HCA-7 tumors in vivo was low and similar to that of muscle, used as reference tissue. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text