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.