在一种新的表达人钠/碘同向转运体（hNIS）的结肠癌细胞系HCT116中，评估[18F] - 四氟硼酸盐作为人钠/碘同向转运体潜在PET成像剂的情况。
Evaluation of [18F]-tetrafluoroborate as a potential PET imaging agent for the human sodium/iodide symporter in a new colon carcinoma cell line, HCT116, expressing hNIS.
作者信息
Weeks Amanda J, Jauregui-Osoro Maite, Cleij Marcel, Blower Julia E, Ballinger James R, Blower Philip J
机构信息
Division of Imaging Sciences, King's College London, St Thomas' Hospital, London, UK.
出版信息
Nucl Med Commun. 2011 Feb;32(2):98-105. doi: 10.1097/MNM.0b013e3283419540.
PURPOSE
Accumulation of iodide and other substrates via the human sodium/iodide symporter (hNIS) is fundamental to imaging and therapy of thyroid disease, hNIS reporter gene imaging and hNIS-mediated gene therapy. There is no readily available positron emission tomography (PET) tracer for hNIS. Our aim was to develop a colon carcinoma cell line stably expressing hNIS, and use it to evaluate a novel hNIS PET tracer, [18F]-tetrafluoroborate.
METHODS
Colon carcinoma cell line, HCT116, was stably transfected with hNIS, thus producing a cell line, HCT116-C19, with high hNIS expression. A Fisher rat thyroid cell line, FRTL5, which expresses rat sodium/iodide symporter when stimulated with thyroid-stimulating hormone, was used for comparison. Accumulation of [188Re]-perrhenate, [99mTc]-pertechnetate and [18F]-tetrafluoroborate was evaluated with and without perchlorate inhibition using an automated radioimmune assay system, LigandTracer. The affinity of [18F]-tetrafluoroborate for hNIS, and its half-maximal inhibitory concentration (IC50) for the inhibition of [99mTc]-pertechnetate transport were determined from the plateau accumulation of [18F]-tetrafluoroborate and [99mTc]-pertechnetate, respectively, as a function of tetrafluoroborate concentration.
RESULTS
[18F]-tetrafluoroborate accumulated effectively in both FRTL5 and HCT116-C19 cells. The accumulation in HCT116-C19 cells (plateau accumulation 31%) was comparable to that of [188Re]-perrhenate (41%) and [99mTc]-pertechnetate (46%). Its affinity for hNIS and half-maximal inhibitory concentration (IC50) for the inhibition of pertechnetate uptake was approximately micromolar.
CONCLUSION
We have produced a human colon cell line with a stable constitutive expression of functional hNIS (HCT116-hNIS-C19). [18F]-tetrafluoroborate accumulates in cells expressing hNIS or rat sodium/iodide symporter and is a potential PET imaging agent in thyroid disease and hNIS reporter gene imaging.
目的
通过人钠/碘同向转运体（hNIS）积累碘化物和其他底物是甲状腺疾病的成像和治疗、hNIS报告基因成像及hNIS介导的基因治疗的基础。目前尚无现成的用于hNIS的正电子发射断层扫描（PET）示踪剂。我们的目的是构建稳定表达hNIS的结肠癌细胞系，并利用其评估新型hNIS PET示踪剂[18F] - 四氟硼酸盐。
方法
将结肠癌细胞系HCT116用hNIS稳定转染，从而产生hNIS高表达的细胞系HCT116 - C19。将受促甲状腺激素刺激时表达大鼠钠/碘同向转运体的Fisher大鼠甲状腺细胞系FRTL5用于对照。使用自动放射免疫分析系统LigandTracer，在有无高氯酸盐抑制的情况下评估[188Re] - 高铼酸盐、[99mTc] - 高锝酸盐和[18F] - 四氟硼酸盐的摄取。分别根据[18F] - 四氟硼酸盐和[99mTc] - 高锝酸盐的平台期摄取量作为四氟硼酸盐浓度的函数，确定[18F] - 四氟硼酸盐对hNIS的亲和力及其对[99mTc] - 高锝酸盐转运抑制的半数最大抑制浓度（IC50）。
结果
[18F] - 四氟硼酸盐在FRTL5和HCT116 - C19细胞中均有效积累。在HCT116 - C19细胞中的积累（平台期积累量为31%）与[188Re] - 高铼酸盐（41%）和[99mTc] - 高锝酸盐（46%）相当。其对hNIS的亲和力及其对高锝酸盐摄取抑制的半数最大抑制浓度（IC50）约为微摩尔级别。
结论
我们构建了具有功能性hNIS稳定组成性表达的人结肠细胞系（HCT116 - hNIS - C19）。[18F] - 四氟硼酸盐在表达hNIS或大鼠钠/碘同向转运体的细胞中积累，是甲状腺疾病和hNIS报告基因成像中的一种潜在PET成像剂。
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