PET radiotracer [18F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation
| Autor: | Jashim Uddin, Antonio Scilimati, Paola Malerba, Mike Nickels, Brenda C. Crews, H. Charles Manning, Maria Grazia Perrone, Mohammed N. Tantawy, Cristina K. Daniel, Paola Vitale, Kebreab Ghebreselasie, Andrea Panella, Lawrence J. Marnett |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty Fluorine Radioisotopes Cell Article chemistry.chemical_compound Mice In vivo Ovarian carcinoma Cell Line Tumor Drug Discovery medicine Biomarkers Tumor Animals Humans Cyclooxygenase Inhibitors Radioactive Tracers Furans IC50 Pharmacology Ovarian Neoplasms Radiochemistry Organic Chemistry Cancer General Medicine Isoxazoles medicine.disease medicine.anatomical_structure Cell Transformation Neoplastic chemistry Positron-Emission Tomography Cancer research Cyclooxygenase 1 Biomarker (medicine) Female Ovarian cancer Tomography X-Ray Computed Lead compound |
| Popis: | Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([(18/19)F]-P6) is the most promising derivative [IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[(18)F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K(18)F/Kryptofix 2.2.2 complex, that afforded [(18)F]-P6 in good radiochemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [(18)F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [(18)F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1. |
| Databáze: | OpenAIRE |
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