Uptake of [¹⁸F]tetrafluoroborate in MCF-7 Breast Cancer Cells is Induced after Stimulation of the Sodium Iodide Symporter.

Abstract

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 [18F]tetrafluoroborate ([18F]TFB) in the endogenously hNIS-expressing breast cancer cell line MCF-7 after an improved radiosynthesis and pharmacological stimulation.

METHODS:

[18F]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 [131I]iodide and [99mTc]pertechnetate. Specificity of the tracer accumulation was assessed by inhibition experiments using NaBF4, KSO3F, KI and KIO3.

RESULTS:

[18F]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 [18F]TFB uptake into the cells (up to 58-fold) as compared to control experiments. Inhibition studies using various NIS-substrates confirmed the specificity of [18F]TFB for hNIS.

CONCLUSION:

[18F]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.

• Authors: Marc Lehmacher, Antje Stolzenburg, Samuel Samnick
• Journal: Current cancer drug targets (Curr Cancer Drug Targets) Vol. 20 Issue 2 Pg. 146-155 ( 2020) ISSN: 1873-5576 [Electronic] Netherlands
• PMID: 32056515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Borates
• Fluorine Radioisotopes
• Radiopharmaceuticals
• Symporters
• sodium-iodide symporter
• Tretinoin
• fluoroboric acid

Topics

• Borates (chemical synthesis, pharmacokinetics)
• Female
• Fluorine Radioisotopes (pharmacokinetics)
• Humans
• MCF-7 Cells
• Radiopharmaceuticals (pharmacokinetics)
• Symporters (analysis, physiology)
• Tretinoin (pharmacology)