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

Author(s): Marc Lehmacher*, Antje Stolzenburg, Samuel Samnick

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 2 , 2020

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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.

Keywords: Sodium iodide symporter (NIS), [18F]tetrafluoroborate, [18F]TFB, breast cancer, MCF-7, PET-imaging.

[1]
Carrasco, N. Iodide transport in the thyroid gland. Biochim. Biophys. Acta, 1993, 1154(1), 65-82.
[http://dx.doi.org/10.1016/0304-4157(93)90017-I] [PMID: 8507647]
[2]
Dai, G.; Levy, O.; Carrasco, N. Cloning and characterization of the thyroid iodide transporter. Nature, 1996, 379(6564), 458-460.
[http://dx.doi.org/10.1038/379458a0] [PMID: 8559252]
[3]
Smanik, P.A.; Liu, Q.; Furminger, T.L.; Ryu, K.; Xing, S.; Mazzaferri, E.L.; Jhiang, S.M. Cloning of the human sodium iodide symporter. Biochem. Biophys. Res. Commun., 1996, 226(2), 339-345.
[http://dx.doi.org/10.1006/bbrc.1996.1358] [PMID: 8806637]
[4]
Smanik, P.A.; Ryu, K.Y.; Theil, K.S.; Mazzaferri, E.L.; Jhiang, S.M. Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter. Endocrinology, 1997, 138(8), 3555-3558.
[http://dx.doi.org/10.1210/endo.138.8.5262] [PMID: 9231811]
[5]
Eskandari, S.; Loo, D.D.; Dai, G.; Levy, O.; Wright, E.M.; Carrasco, N. Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. J. Biol. Chem., 1997, 272(43), 27230-27238.
[http://dx.doi.org/10.1074/jbc.272.43.27230] [PMID: 9341168]
[6]
Dohán, O.; Portulano, C.; Basquin, C.; Reyna-Neyra, A.; Amzel, L.M.; Carrasco, N. The Na+/I- symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate. Proc. Natl. Acad. Sci. USA, 2007, 104(51), 20250-20255.
[http://dx.doi.org/10.1073/pnas.0707207104] [PMID: 18077370]
[7]
Youn, H.; Jeong, J.M.; Chung, J-K. A new PET probe, 18F-tetrafluoroborate, for the sodium/iodide symporter: Possible impacts on nuclear medicine. Eur. J. Nucl. Med. Mol. Imaging, 2010, 37(11), 2105-2107.
[http://dx.doi.org/10.1007/s00259-010-1601-3] [PMID: 20821208]
[8]
Tazebay, U.H.; Wapnir, I.L.; Levy, O.; Dohan, O.; Zuckier, L.S.; Zhao, Q.H.; Deng, H.F.; Amenta, P.S.; Fineberg, S.; Pestell, R.G.; Carrasco, N. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat. Med., 2000, 6(8), 871-878.
[http://dx.doi.org/10.1038/78630] [PMID: 10932223]
[9]
Nakamoto, Y.; Saga, T.; Misaki, T.; Kobayashi, H.; Sato, N.; Ishimori, T.; Kosugi, S.; Sakahara, H.; Konishi, J. Establishment and characterization of a breast cancer cell line expressing Na+/I- symporters for radioiodide concentrator gene therapy. J. Nucl. Med., 2000, 41(11), 1898-1904.
[PMID: 11079502]
[10]
Kilbane, M.T.; Ajjan, R.A.; Weetman, A.P.; Dwyer, R.; McDermott, E.W.; O’Higgins, N.J.; Smyth, P.P. Tissue iodine content and serum-mediated 125i uptake-blocking activity in breast cancer. J. Clin. Endocrinol. Metab., 2000, 85(3), 1245-1250.
[http://dx.doi.org/10.1210/jc.85.3.1245] [PMID: 10720070]
[11]
Rudnicka, L.; Sińczak, A.; Szybiński, P.; Huszno, B.; Stachura, J. Expression of the Na(+)/I- symporter in invasive ductal breast cancer. Folia Histochem. Cytobiol., 2003, 41(1), 37-40.
[PMID: 12705478]
[12]
Upadhyay, G.; Singh, R.; Agarwal, G.; Mishra, S.K.; Pal, L.; Pradhan, P.K.; Das, B.K.; Godbole, M.M. Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue. Breast Cancer Res. Treat., 2003, 77(2), 157-165.
[http://dx.doi.org/10.1023/A:1021321409159] [PMID: 12602914]
[13]
Wapnir, I.L.; van de Rijn, M.; Nowels, K.; Amenta, P.S.; Walton, K.; Montgomery, K.; Greco, R.S.; Dohán, O.; Carrasco, N. Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. J. Clin. Endocrinol. Metab., 2003, 88(4), 1880-1888.
[http://dx.doi.org/10.1210/jc.2002-021544] [PMID: 12679487]
[14]
Titcomb, M.W.; Gottardis, M.M.; Pike, J.W.; Allegretto, E.A. Sensitive and specific detection of retinoid receptor subtype proteins in cultured cell and tumor extracts. Mol. Endocrinol., 1994, 8(7), 870-877.
[http://dx.doi.org/10.1210/mend.8.7.7984149] [PMID: 7984149]
[15]
Evans, T.R.; Kaye, S.B. Retinoids: Present role and future potential. Br. J. Cancer, 1999, 80(1-2), 1-8.
[http://dx.doi.org/10.1038/sj.bjc.6690312] [PMID: 10389969]
[16]
Kogai, T.; Schultz, J.J.; Johnson, L.S.; Huang, M.; Brent, G.A. Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line. Proc. Natl. Acad. Sci. USA, 2000, 97(15), 8519-8524.
[http://dx.doi.org/10.1073/pnas.140217197] [PMID: 10890895]
[17]
Kogai, T.; Kanamoto, Y.; Che, L.H.; Taki, K.; Moatamed, F.; Schultz, J.J.; Brent, G.A. Systemic retinoic acid treatment induces sodium/iodide symporter expression and radioiodide uptake in mouse breast cancer models. Cancer Res., 2004, 64(1), 415-422.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-2285] [PMID: 14729653]
[18]
Kogai, T.; Kanamoto, Y.; Li, A.I.; Che, L.H.; Ohashi, E.; Taki, K.; Chandraratna, R.A.; Saito, T.; Brent, G.A. Differential regulation of sodium/iodide symporter gene expression by nuclear receptor ligands in MCF-7 breast cancer cells. Endocrinology, 2005, 146(7), 3059-3069.
[http://dx.doi.org/10.1210/en.2004-1334] [PMID: 15817668]
[19]
Unterholzner, S.; Willhauck, M.J.; Cengic, N.; Schuetz, M.; Goeke, B.; Morris, J.C.; Spitzweg, C. Dexamethasone stimulation of retinoic Acid-induced sodium iodide symporter expression and cytotoxicity of 131-I in breast cancer cells. J. Clin. Endocrinol. Metab., 2006, 91(1), 69-78.
[http://dx.doi.org/10.1210/jc.2005-0779] [PMID: 16234306]
[20]
Anbar, M.; Guttmann, S.; Lewitus, Z. Effect of monofluorosulphonate, difluorophosphate and fluoroborate ions on the iodine uptake of the thyroid gland. Nature, 1959, 183(4674), 1517-1518.
[http://dx.doi.org/10.1038/1831517a0] [PMID: 13666792]
[21]
Anbar, M.; Guttmann, S.; Lewitus, Z. The accumulation of fluoroborate ions in thyroid glands of rats. Endocrinology, 1960, 66, 888-890.
[http://dx.doi.org/10.1210/endo-66-6-888] [PMID: 13793273]
[22]
Jauregui-Osoro, M.; Sunassee, K.; Weeks, A.J.; Berry, D.J.; Paul, R.L.; Cleij, M.; Banga, J.P.; O’Doherty, M.J.; Marsden, P.K.; Clarke, S.E.M.; Ballinger, J.R.; Szanda, I.; Cheng, S-Y.; Blower, P.J. Synthesis and biological evaluation of [18F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter. Eur. J. Nucl. Med. Mol. Imaging, 2010, 37(11), 2108-2116.
[http://dx.doi.org/10.1007/s00259-010-1523-0] [PMID: 20577737]
[23]
Weeks, A.J.; Jauregui-Osoro, M.; Cleij, M.; Blower, J.E.; Ballinger, J.R.; Blower, P.J. 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. Nucl. Med. Commun., 2011, 32(2), 98-105.
[http://dx.doi.org/10.1097/MNM.0b013e3283419540] [PMID: 21085047]
[24]
Khoshnevisan, A.; Jauregui-Osoro, M.; Shaw, K.; Torres, J.B.; Young, J.D.; Ramakrishnan, N.K.; Jackson, A.; Smith, G.E.; Gee, A.D.; Blower, P.J. [18F]tetrafluoroborate as a PET tracer for the sodium/iodide symporter: the importance of specific activity. EJNMMI Res., 2016, 6(1), 34.
[http://dx.doi.org/10.1186/s13550-016-0188-5] [PMID: 27103614]
[25]
Jiang, H.; Bansal, A.; Pandey, M.K.; Peng, K-W.; Suksanpaisan, L.; Russell, S.J.; DeGrado, T.R. Synthesis of 18F-tetrafluoroborate via radiofluorination of boron trifluoride and evaluation in a murine C6-glioma tumor model. J. Nucl. Med., 2016, 57(9), 1454-1459.
[http://dx.doi.org/10.2967/jnumed.115.170894] [PMID: 27103021]
[26]
Samnick, S.; Al-Momani, E.; Schmid, J-S.; Mottok, A.; Buck, A.K.; Lapa, C. Initial clinical investigation of [18F]Tetrafluoro-borate PET/CT in comparison to [124I]Iodine PET/CT for imaging thyroid cancer. Clin. Nucl. Med., 2018, 43(3), 162-167.
[http://dx.doi.org/10.1097/RLU.0000000000001977] [PMID: 29356744]
[27]
Coenen, H.H.; Gee, A.D.; Adam, M.; Antoni, G.; Cutler, C.S.; Fujibayashi, Y.; Jeong, J.M.; Mach, R.H.; Mindt, T.L.; Pike, V.W.; Windhorst, A.D. Consensus nomenclature rules for radiopharmaceutical chemistry - Setting the record straight. Nucl. Med. Biol., 2017, 55, v-xi.
[http://dx.doi.org/10.1016/j.nucmedbio.2017.09.004] [PMID: 29074076]
[28]
Marti-Climent, J.M.; Collantes, M.; Jauregui-Osoro, M.; Quincoces, G.; Prieto, E.; Bilbao, I.; Ecay, M.; Richter, J.A.; Peñuelas, I. Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [18F]-tetrafluoroborate. EJNMMI Res., 2015, 5(1), 70.
[http://dx.doi.org/10.1186/s13550-015-0148-5] [PMID: 26635227]
[29]
Moon, D.H.; Lee, S.J.; Park, K.Y.; Park, K.K.; Ahn, S.H.; Pai, M.S.; Chang, H.; Lee, H.K.; Ahn, I-M. Correlation between 99mTc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues. Nucl. Med. Biol., 2001, 28(7), 829-834.
[http://dx.doi.org/10.1016/S0969-8051(01)00243-8] [PMID: 11578905]
[30]
Beyer, S.J.; Jimenez, R.E.; Shapiro, C.L.; Cho, J.Y.; Jhiang, S.M. Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer? Breast Cancer Res. Treat., 2009, 115(1), 205-212.
[http://dx.doi.org/10.1007/s10549-008-0059-5] [PMID: 18500672]


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VOLUME: 20
ISSUE: 2
Year: 2020
Page: [146 - 155]
Pages: 10
DOI: 10.2174/1568009619666191016145602
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