Uptake of [<sup>18</sup>F]tetrafluoroborate in MCF-7 Breast Cancer Cells is Induced after Stimulation of the Sodium Iodide Symporter / Marc Lehmacher, Antje Stolzenburg, Samuel Samnick
Background: The human sodium iodide symporter (hNIS) has been the most important target in nuclear medicine regarding thyroid-related diseases. Although hNIS-expression can also be determined in extra-thyroidal tumors, imaging hNIS with positron emission tomography has not been exploited clinically. Objective: Here, we evaluated the accumulation of the novel hNIS-substrate [ 18 F]tetrafluoroborate ([ 18 F]TFB) in the endogenously hNIS-expressing breast cancer cell line MCF-7 after an improved radiosynthesis and pharmacological stimulation. Methods: [ 18 F]TFB was prepared under mild reaction conditions (40°C, 25 min) and its uptake properties were investigated in MCF-7 cells pretreated with a combination of all-trans retinoic acid plus methasone-derivatives and compared to the clinically established tracers [ 131 I]iodide and [ 99m Tc]pertechnetate. Specificity of the tracer accumulation was assessed by inhibition experiments using NaBF 4 , KSO 3 F, KI and KIO 3 . Results:[ 18 F]TFB was obtained with a radiochemical yield of 24.0 ± 6.6 % (n = 17) within 40 min after high pressure liquid chromatography-separation and with 26.8 ± 6.2 % (n = 13) within 45 min after adapting the procedure on a synthesis module using higher starting activities (> 10 GBq). After pharmacological treatment, a 4-fold increase in hNIS-expression on the MCF-7 cell surface was achieved, resulting in a significantly higher [ 18 F]TFB uptake into the cells (up to 58-fold) as compared to control experiments. Inhibition studies using various NIS-substrates confirmed the specificity of [ 18 F]TFB for hNIS. Conclusion: [ 18 F]TFB was shown to be a promising hNIS-substrate in our model using the human MCF-7 breast cancer cell line mandating in vivo evaluations in xenografted studies and in patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Current cancer drug targets - 20(2020), 2, Seite 10 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lehmacher, Marc [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Umfang: |
1 Online-Ressource (10 p) |
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| Förderinstitution / Projekttitel: |
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KFL011142936 |
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| 245 | 1 | 0 | |a Uptake of [<sup>18</sup>F]tetrafluoroborate in MCF-7 Breast Cancer Cells is Induced after Stimulation of the Sodium Iodide Symporter |c Marc Lehmacher, Antje Stolzenburg, Samuel Samnick |
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| 520 | |a Background: The human sodium iodide symporter (hNIS) has been the most important target in nuclear medicine regarding thyroid-related diseases. Although hNIS-expression can also be determined in extra-thyroidal tumors, imaging hNIS with positron emission tomography has not been exploited clinically. Objective: Here, we evaluated the accumulation of the novel hNIS-substrate [ 18 F]tetrafluoroborate ([ 18 F]TFB) in the endogenously hNIS-expressing breast cancer cell line MCF-7 after an improved radiosynthesis and pharmacological stimulation. Methods: [ 18 F]TFB was prepared under mild reaction conditions (40°C, 25 min) and its uptake properties were investigated in MCF-7 cells pretreated with a combination of all-trans retinoic acid plus methasone-derivatives and compared to the clinically established tracers [ 131 I]iodide and [ 99m Tc]pertechnetate. Specificity of the tracer accumulation was assessed by inhibition experiments using NaBF 4 , KSO 3 F, KI and KIO 3 . Results:[ 18 F]TFB was obtained with a radiochemical yield of 24.0 ± 6.6 % (n = 17) within 40 min after high pressure liquid chromatography-separation and with 26.8 ± 6.2 % (n = 13) within 45 min after adapting the procedure on a synthesis module using higher starting activities (> 10 GBq). After pharmacological treatment, a 4-fold increase in hNIS-expression on the MCF-7 cell surface was achieved, resulting in a significantly higher [ 18 F]TFB uptake into the cells (up to 58-fold) as compared to control experiments. Inhibition studies using various NIS-substrates confirmed the specificity of [ 18 F]TFB for hNIS. Conclusion: [ 18 F]TFB was shown to be a promising hNIS-substrate in our model using the human MCF-7 breast cancer cell line mandating in vivo evaluations in xenografted studies and in patients | ||
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