Department of Nuclear Medicine, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
Curr Cancer Drug Targets. 2020;20(2):146-155. doi: 10.2174/1568009619666191016145602.
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.
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.
[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.
[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.
[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.
人类钠碘转运体（hNIS）一直是核医学中甲状腺相关疾病最重要的靶点。尽管 hNIS 的表达也可以在甲状腺外肿瘤中确定，但用正电子发射断层扫描术（PET）对 hNIS 进行成像尚未在临床上得到应用。
本研究通过改进的放射合成和药理刺激，评估新型 hNIS 底物[18F]四氟硼酸（[18F]TFB）在天然 hNIS 表达的乳腺癌细胞系 MCF-7 中的积累。
在温和的反应条件（40°C，25 分钟）下制备[18F]TFB，并研究其在经过全反式视黄酸加甲泼尼龙衍生物联合预处理的 MCF-7 细胞中的摄取特性，并与临床应用的示踪剂[131I]碘化物和[99mTc]高锝酸盐进行比较。通过使用 NaBF4、KSO3F、KI 和 KIO3 进行抑制实验，评估示踪剂积累的特异性。
经过高效液相色谱分离后，[18F]TFB 的放射化学产率为 24.0±6.6%（n=17），在 40 分钟内获得；在合成模块上适应更高的起始活性（>10GBq）后，在 45 分钟内获得[18F]TFB 的放射化学产率为 26.8±6.2%（n=13）。经过药理处理后，MCF-7 细胞表面 hNIS 的表达增加了 4 倍，导致细胞内[18F]TFB 的摄取显著增加（高达 58 倍），与对照实验相比。使用各种 NIS 底物的抑制研究证实了[18F]TFB 对 hNIS 的特异性。
在我们使用人 MCF-7 乳腺癌细胞系的模型中，[18F]TFB 被证明是一种有前途的 hNIS 底物，需要在异种移植研究和患者中进行体内评估。
