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Evaluation of MR relaxation times following trastuzumab treatment of breast cancer cells in a 3D bioreactor

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Bartusik-Aebisher D., Aebisher D., Czmil A., Mazur D.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 1
35-41
EN
The three dimensional tumor environment can be mimicked with the use of cells cultured within a hollow-fiber bioreactor (HFBR). In this work, magnetic resonance imaging (MRI) was used to monitor changes in relaxation time in breast cancer cells following treatment with Trastuzumab in a HFBR system. Breast cancer cells were inoculated into the HFBR system and cultured over a period of 4 weeks. Relaxation time maps were generated according to MRI techniques in three dimensional (3D) cultures of MCF7/Her2 breast cancer and MCF7/Neo4 control cells. MRI measurements showed a variation in values of spin-lattice (T1) and spin-spin (T2) relaxation times related to cell density. Differences in both values (T1 and T2) were noted between untreated cells and cells treated with trastuzumab in the HFBR device. Additionally, 1H MRI was able to provide information about drug penetration in breast cancer cell culture organized in 3D. In conclusion, MRI in vitro can provide direct, noninvasive visualization of cell density in 3D geometry and cell viability as a function of drug uptake. Both T1 and T2 values were higher for lower cell density and accordingly both values, T1 and T2, were lower for higher cell density.
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Trastuzumab Efficacy Quantified by Fluorine-19 Magnetic Resonance Imaging

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Bartusik-Aebisher D., Aebisher D., Czmil M. A., Mazur D.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 3
495-503
EN
The purpose of this study was to conjugate Trastuzumab with fluorine-bearing PAMAM dendrimer to compare activities in three-dimensional (3D) cultured breast cancer cells with parent Trastuzumab. An in vitro study was performed to determine cellular responses to fluorinated Trastuzumab conjugates by Magnetic Resonance Imaging (MRI). Breast cancer cells were cultured in 3D geometry. Proton (1H) MRI and Fluorine-19 (19F) MRI were used for visualization of cellular locations within a Hollow Fiber Bioreactor (HFBR) device and to monitor the cellular response to treatment. The results of this study confirm that cell growth is significantly decreased following treatment with Trastuzumab conjugates. The use of fluorinated Trastuzumab conjugates decreases breast cancer cell growth in 3D cultures and allows for tracking of drug delivery to cancer cells via 19F.
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