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Application of F magnetic resonance to study the efficacy of fluorine labeled drugs in the three-dimensional cultured breast cancer cells |
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| Authors: | Dorota Bartusik Boguslaw Tomanek |
| Affiliation: | a National Research Council Canada, Institute for Biodiagnostics (West), 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1 b Cross Cancer Institute, Department of Medical Physics, 11560 University Ave., Edmonton, Alberta, Canada T6G 1Z2 c Institute of Nuclear Physics, Polish Academy of Sciences, Radzikowskiego 152, 31-342 Krakow, Poland d University of Alberta, Department of Oncology, 11560 University Ave, Edmonton, Alberta, Canada T6G 1Z2 |
| Abstract: | The cellular monitoring of tumor response to treatments is important for drug discovery and drug development in cancer therapy. We studied efficacy of Herceptin, a common breast cancer drug conjugated with a fluorine organic compound, perfluoro-15-crown-5-ether (PFCE) which easily forms biocompatible emulsions. Three new pharmaceutical forms of Herceptin, Herceptin/PFCE, Herceptin/PFCE/Lipoplex and Herceptin/PFCE/HydraLink were synthesized for the ex vivo study of their efficacy in breast cancer treatment. The emulsions were administered to 109 cells mL−1 of HER-2 positive human adenocarcinoma (MCF-7) cells and the same amount of human mammary epithelial cells (HMEC) cultured in three-dimensional (3D) geometry using hollow fiber bioreactor (HFB) device. Following drugs administration ex vivo, fluorine-19 magnetic resonance imaging (19F MRI) was applied for cells imaging to measure their viability and to study drug efficacy over 72 h. To ensure optimum drug tracking, HydraLink was used to provide stable binding affinity of emulsified Herceptin to receptor while cationic lipid (Lipofectamine) was used to enhance lipophilicity of the emulsions.After 72 h of treatment with Herceptin, Herceptin/PFCE, Herceptin/PFCE/Lipoplex and Herceptin/PFCE/HydraLink the viability of cells was 54 ± 2%, 49 ± 3%, 43 ± 5% and 42 ± 1%, respectively, as compared with control 93 ± 2%. The efficacy (EC50) of Herceptin conjugated with emulsions was found to be 970 ± 13 μg mL−1 for Herceptin/PFCE, 645 ± 11 μg mL−1 for Herceptin/PFCE/Lipoplex, 678 ± 7 μg mL−1 for Herceptin/PFCE/HydraLink and 1000 ± 3 μg mL−1 for Herceptin. The results show that fluorine emulsions improved the efficacy of Herceptin and 19F signal intensity changes validated drug efficiency. The significant correlations between duration of treatments and MCF-7 cells viability were observed. While we studied breast cancer cells, the fluorine emulsions could be applied for treatment of other cancer cells overexpressing HER-2. |
| Keywords: | Fluorine magnetic resonance imaging Breast cancer cells |
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