In vivo Radioiodide Imaging and Treatment of Breast Cancer Xenografts after MUC1-Driven Expression of the Sodium Iodide Symporter

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. Conclusions: [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.

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Bone Marrow Mesenchymal Stem Cell mediated Ultrasmall Gold Nanoclusters and hNIS Gene Synergize Radiotherapy in Breast Cancer

Journal of Materials Chemistry B ◽

10.1039/d1tb00186h ◽

2021 ◽

Author(s):

Lu Zhang ◽

Benchao Zheng ◽

Rui Guo ◽

Ying Miao ◽

Biao Li

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Stem Cell ◽

Growth Response ◽

Sodium Iodide ◽

Gold Nanoclusters ◽

Early Growth ◽

Sodium Iodide Symporter ◽

Early Growth Response ◽

131I Treatment

The human sodium iodide symporter (hNIS) can be linked to the downstream of radiation-sensitive early growth response protein1 (Egr1) promoter, and activated by the Egr1 following 131I treatment. However, the...

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Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine

Journal of Endocrinology ◽

10.1677/joe.1.05643 ◽

2005 ◽

Vol 184 (1) ◽

pp. 69-76 ◽

Cited By ~ 50

Author(s):

Andrea C F Ferreira ◽

Lívia P Lima ◽

Renata L Araújo ◽

Glaucia Müller ◽

Renata P Rocha ◽

...

Keyword(s):

Sodium Iodide ◽

Iodine Content ◽

Concomitant Administration ◽

High Serum ◽

Sodium Iodide Symporter ◽

Physiological Control ◽

Iodide Uptake ◽

Thyroid Hormone Biosynthesis ◽

Serum Tsh

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium–iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0.05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

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In vivo long-term imaging and radioiodine therapy by sodium-iodide symporter gene expression using a lentiviral system containing ubiquitin C promoter

Cancer Biology & Therapy ◽

10.4161/cbt.6.7.4342 ◽

2007 ◽

Vol 6 (7) ◽

pp. 1130-1135 ◽

Cited By ~ 18

Author(s):

Hyun Joo Kim ◽

Yong Hyun Jeon ◽

Joo Hyun Kang ◽

Yong Jin Lee ◽

Kwang Kim ◽

...

Keyword(s):

Gene Expression ◽

Sodium Iodide ◽

Radioiodine Therapy ◽

Sodium Iodide Symporter

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The importance of sodium/iodide symporter (NIS) for thyroid cancer management

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302007000500004 ◽

2007 ◽

Vol 51 (5) ◽

pp. 672-682 ◽

Cited By ~ 36

Author(s):

Denise P. Carvalho ◽

Andrea C.F. Ferreira

Keyword(s):

Sodium Iodide ◽

Sodium Iodide Symporter ◽

Therapeutic Tool ◽

Iodide Transport ◽

Cancer Management ◽

Thyroid Hormone Biosynthesis ◽

Nis Gene ◽

Hormone Biosynthesis ◽

Tumoral Cells

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.

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