Application of 19F magnetic resonance to study the efficacy of fluorine labeled drugs in the three-dimensional cultured breast cancer cells

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DOIResolve DOI: http://doi.org/10.1016/j.abb.2009.11.003
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TypeArticle
Journal titleArchives of Biochemistry and Biophysics
Volume493
Issue2
Pages234241; # of pages: 8
SubjectFluorine magnetic resonance imaging; Breast cancer cells
AbstractThe 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.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biodiagnostics; National Research Council Canada
Peer reviewedYes
NPARC number17326683
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Record identifier2e5f4b15-4561-4c1f-9b5c-8d122a68827f
Record created2011-04-03
Record modified2016-05-09
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