The sodium iodide symporter (NIS) as theranostic gene: its emerging role in new imaging modalities and non-viral gene therapy

Springer Science and Business Media LLC - Tập 12 - Trang 1-14 - 2022
Carolin Kitzberger1, Rebekka Spellerberg1, Volker Morath2, Nathalie Schwenk1, Kathrin A. Schmohl1, Christina Schug1, Sarah Urnauer1, Mariella Tutter1, Matthias Eiber2, Franz Schilling2, Wolfgang A. Weber2, Sibylle Ziegler3, Peter Bartenstein3, Ernst Wagner4, Peter J. Nelson1, Christine Spitzweg1,5
1Department of Internal Medicine IV, University Hospital LMU Munich, Munich, Germany
2Department of Nuclear Medicine, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
3Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
4Pharmaceutical Biotechnology, Department of Pharmacy, Centre for System-Based Drug Research, and Centre for Nanoscience, LMU Munich, Munich, Germany
5Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, USA

Tóm tắt

Cloning of the sodium iodide symporter (NIS) in 1996 has provided an opportunity to use NIS as a powerful theranostic transgene. Novel gene therapy strategies rely on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of therapeutic radionuclides. This review highlights the remarkable progress during the last two decades in the development of the NIS gene therapy concept using selective non-viral gene delivery vehicles including synthetic polyplexes and genetically engineered mesenchymal stem cells. In addition, NIS is a sensitive reporter gene and can be monitored by high resolution PET imaging using the radiotracers sodium [124I]iodide ([124I]NaI) or [18F]tetrafluoroborate ([18F]TFB). We performed a small preclinical PET imaging study comparing sodium [124I]iodide and in-house synthesized [18F]TFB in an orthotopic NIS-expressing glioblastoma model. The results demonstrated an improved image quality using [18F]TFB. Building upon these results, we will be able to expand the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumor models with low volume disease, such as glioblastoma. Trial registration not applicable.

Tài liệu tham khảo

De La Vieja A, Dohan O, Levy O, Carrasco N. Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology. Physiol Rev. 2000;80(3):1083–105. Hingorani M, Spitzweg C, Vassaux G, Newbold K, Melcher A, Pandha H, et al. The biology of the sodium iodide symporter and its potential for targeted gene delivery. Curr Cancer Drug Targets. 2010;10(2):242–67. Llorente-Esteban A, Manville RW, Reyna-Neyra A, Abbott GW, Amzel LM, Carrasco N. Allosteric regulation of mammalian Na(+)/I(-) symporter activity by perchlorate. Nat Struct Mol Biol. 2020;27(6):533–9. Spitzweg C, Bible KC, Hofbauer LC, Morris JC. Advanced radioiodine-refractory differentiated thyroid cancer: the sodium iodide symporter and other emerging therapeutic targets. Lancet Diabetes Endocrinol. 2014;2(10):830–42. Spitzweg C, Nelson PJ, Wagner E, Bartenstein P, Weber WA, Schwaiger M, et al. The sodium iodide symporter (NIS): novel applications for radionuclide imaging and treatment. Endocr Relat Cancer. 2021;28(10):T193–213. Willhauck MJ, Sharif Samani BR, Gildehaus FJ, Wolf I, Senekowitsch-Schmidtke R, Stark HJ, et al. Application of 188rhenium as an alternative radionuclide for treatment of prostate cancer after tumor-specific sodium iodide symporter gene expression. J Clin Endocrinol Metab. 2007;92(11):4451–8. Willhauck MJ, Samani BR, Wolf I, Senekowitsch-Schmidtke R, Stark HJ, Meyer GJ, et al. The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35(7):1272–81. Dadachova E, Bouzahzah B, Zuckier LS, Pestell RG. Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS). Nucl Med Biol. 2002;29(1):13–8. Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 1996;379(6564):458–60. Shimura H, Haraguchi K, Miyazaki A, Endo T, Onaya T. Iodide uptake and experimental 131I therapy in transplanted undifferentiated thyroid cancer cells expressing the Na+/I- symporter gene. Endocrinology. 1997;138(10):4493–6. Hager S, Wagner E. Bioresponsive polyplexes—chemically programmed for nucleic acid delivery. Expert Opin Drug Deliv. 2018;15(11):1067–83. Klutz K, Schaffert D, Willhauck MJ, Grunwald GK, Haase R, Wunderlich N, et al. Epidermal growth factor receptor-targeted (131)I-therapy of liver cancer following systemic delivery of the sodium iodide symporter gene. Mol Ther. 2011;19(4):676–85. Lachelt U, Wagner E. Nucleic acid therapeutics using polyplexes: a journey of 50 years (and beyond). Chem Rev. 2015;115(19):11043–78. Schafer A, Pahnke A, Schaffert D, van Weerden WM, de Ridder CM, Rodl W, et al. Disconnecting the yin and yang relation of epidermal growth factor receptor (EGFR)-mediated delivery: a fully synthetic, EGFR-targeted gene transfer system avoiding receptor activation. Hum Gene Ther. 2011;22(12):1463–73. Schmohl KA, Dolp P, Schug C, Knoop K, Klutz K, Schwenk N, et al. Reintroducing the sodium-iodide symporter to anaplastic thyroid carcinoma. Thyroid. 2017;27(12):1534–43. Schmohl KA, Gupta A, Grunwald GK, Trajkovic-Arsic M, Klutz K, Braren R, et al. Imaging and targeted therapy of pancreatic ductal adenocarcinoma using the theranostic sodium iodide symporter (NIS) gene. Oncotarget. 2017;8(20):33393–404. Urnauer S, Muller AM, Schug C, Schmohl KA, Tutter M, Schwenk N, et al. EGFR-targeted nonviral NIS gene transfer for bioimaging and therapy of disseminated colon cancer metastases. Oncotarget. 2017;8(54):92195–208. He D, Wagner E. Defined polymeric materials for gene delivery. Macromol Biosci. 2015;15(5):600–12. Kos P, Lachelt U, Herrmann A, Mickler FM, Doblinger M, He D, et al. Histidine-rich stabilized polyplexes for cMet-directed tumor-targeted gene transfer. Nanoscale. 2015;7(12):5350–62. Urnauer S, Morys S, Krhac Levacic A, Muller AM, Schug C, Schmohl KA, et al. Sequence-defined cMET/HGFR-targeted polymers as gene delivery vehicles for the theranostic sodium iodide symporter (NIS) gene. Mol Ther. 2016;24(8):1395–404. Urnauer S, Schmohl KA, Tutter M, Schug C, Schwenk N, Morys S, et al. Dual-targeted NIS polyplexes-a theranostic strategy toward tumors with heterogeneous receptor expression. Gene Ther. 2019;26(3–4):93–108. Hagenhoff A, Bruns CJ, Zhao Y, von Luttichau I, Niess H, Spitzweg C, et al. Harnessing mesenchymal stem cell homing as an anticancer therapy. Expert Opin Biol Ther. 2016;16(9):1079–92. Melzer C, Yang Y, Hass R. Interaction of MSC with tumor cells. Cell Commun Signal. 2016;14(1):20. Schmohl KA, Müller AM, Wechselberger A, Rühland S, Salb N, Schwenk N, et al. Thyroid hormones and tetrac: new regulators of tumour stroma formation via integrin αvβ3. Endocr Relat Cancer. 2015;22(6):941–52. Droujinine IA, Eckert MA, Zhao W. To grab the stroma by the horns: from biology to cancer therapy with mesenchymal stem cells. Oncotarget. 2013;4(5):651–64. Niess H, von Einem JC, Thomas MN, Michl M, Angele MK, Huss R, et al. Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial. BMC Cancer. 2015;15:237. Knoop K, Kolokythas M, Klutz K, Willhauck MJ, Wunderlich N, Draganovici D, et al. Image-guided, tumor stroma-targeted 131I therapy of hepatocellular cancer after systemic mesenchymal stem cell-mediated NIS gene delivery. Mol Ther. 2011;19(9):1704–13. Knoop K, Schwenk N, Dolp P, Willhauck MJ, Zischek C, Zach C, et al. Stromal targeting of sodium iodide symporter using mesenchymal stem cells allows enhanced imaging and therapy of hepatocellular carcinoma. Hum Gene Ther. 2013;24(3):306–16. Knoop K, Schwenk N, Schmohl K, Muller A, Zach C, Cyran C, et al. Mesenchymal stem cell-mediated, tumor stroma-targeted radioiodine therapy of metastatic colon cancer using the sodium iodide symporter as theranostic gene. J Nucl Med. 2015;56(4):600–6. Schug C, Gupta A, Urnauer S, Steiger K, Cheung PF, Neander C, et al. A novel approach for image-guided (131)I therapy of pancreatic ductal adenocarcinoma using mesenchymal stem cell-mediated NIS gene delivery. Mol Cancer Res. 2019;17(1):310–20. Muller AM, Schmohl KA, Knoop K, Schug C, Urnauer S, Hagenhoff A, et al. Hypoxia-targeted 131I therapy of hepatocellular cancer after systemic mesenchymal stem cell-mediated sodium iodide symporter gene delivery. Oncotarget. 2016;7(34):54795–810. Schug C, Urnauer S, Jaeckel C, Schmohl KA, Tutter M, Steiger K, et al. TGFB1-driven mesenchymal stem cell-mediated NIS gene transfer. Endocr Relat Cancer. 2019;26(1):89–101. Klopp AH, Spaeth EL, Dembinski JL, Woodward WA, Munshi A, Meyn RE, et al. Tumor irradiation increases the recruitment of circulating mesenchymal stem cells into the tumor microenvironment. Cancer Res. 2007;67(24):11687–95. Schug C, Sievert W, Urnauer S, Muller AM, Schmohl KA, Wechselberger A, et al. External beam radiation therapy enhances mesenchymal stem cell-mediated sodium-iodide symporter gene delivery. Hum Gene Ther. 2018;29(11):1287–300. Schug C, Kitzberger C, Sievert W, Spellerberg R, Tutter M, Schmohl KA, et al. Radiation-induced amplification of TGFB1-induced mesenchymal stem cell-mediated sodium iodide symporter (NIS) gene (131)I therapy. Clin Cancer Res. 2019;25(19):5997–6008. Tutter M, Schug C, Schmohl KA, Urnauer S, Kitzberger C, Schwenk N, et al. Regional hyperthermia enhances mesenchymal stem cell recruitment to tumor stroma: implications for mesenchymal stem cell-based tumor therapy. Mol Ther. 2021;29(2):788–803. Tutter M, Schug C, Schmohl KA, Urnauer S, Schwenk N, Petrini M, et al. Effective control of tumor growth through spatial and temporal control of theranostic sodium iodide symporter (NIS) gene expression using a heat-inducible gene promoter in engineered mesenchymal stem cells. Theranostics. 2020;10(10):4490–506. Ravera S, Reyna-Neyra A, Ferrandino G, Amzel LM, Carrasco N. The sodium/iodide symporter (NIS): molecular physiology and preclinical and clinical applications. Annu Rev Physiol. 2017;79:261–89. Jiang H, DeGrado TR. [(18)F]Tetrafluoroborate ([(18)F]TFB) and its analogs for PET imaging of the sodium/iodide symporter. Theranostics. 2018;8(14):3918–31. Samnick S, Al-Momani E, Schmid JS, Mottok A, Buck AK, Lapa C. Initial clinical investigation of [18F]tetrafluoroborate PET/CT in comparison to [124I]iodine PET/CT for imaging thyroid cancer. Clin Nucl Med. 2018;43(3):162–7. Portulano C, Paroder-Belenitsky M, Carrasco N. The Na+/I- symporter (NIS): mechanism and medical impact. Endocr Rev. 2014;35(1):106–49. Dittmann M, Gonzalez Carvalho JM, Rahbar K, Schafers M, Claesener M, Riemann B, et al. Incremental diagnostic value of [(18)F]tetrafluoroborate PET-CT compared to [(131)I]iodine scintigraphy in recurrent differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2020;47(11):2639–46. Jauregui-Osoro M, Sunassee K, Weeks AJ, Berry DJ, Paul RL, Cleij M, et al. Synthesis and biological evaluation of [(18)F]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):2108–16. Khoshnevisan A, Jauregui-Osoro M, Shaw K, Torres JB, Young JD, Ramakrishnan NK, et al. [(18)F]tetrafluoroborate as a PET tracer for the sodium/iodide symporter: the importance of specific activity. EJNMMI Res. 2016;6(1):34. O’Doherty J, Jauregui-Osoro M, Brothwood T, Szyszko T, Marsden PK, O’Doherty MJ, et al. (18)F-Tetrafluoroborate, a PET probe for imaging sodium/iodide symporter expression: whole-body biodistribution, safety, and radiation dosimetry in thyroid cancer patients. J Nucl Med. 2017;58(10):1666–71. Jiang H, Schmit NR, Koenen AR, Bansal A, Pandey MK, Glynn RB, et al. Safety, pharmacokinetics, metabolism and radiation dosimetry of (18)F-tetrafluoroborate ((18)F-TFB) in healthy human subjects. EJNMMI Res. 2017;7(1):90. Jiang H, Bansal A, Pandey MK, Peng KW, Suksanpaisan L, Russell SJ, et al. Synthesis of 18F-tetrafluoroborate via radiofluorination of boron trifluoride and evaluation in a murine C6-glioma tumor model. J Nucl Med. 2016;57(9):1454–9. Nagarajah J, Le M, Knauf JA, Ferrandino G, Montero-Conde C, Pillarsetty N, et al. Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine. J Clin Investig. 2016;126(11):4119–24. Diocou S, Volpe A, Jauregui-Osoro M, Boudjemeline M, Chuamsaamarkkee K, Man F, et al. [(18)F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model. Sci Rep. 2017;7(1):946. Verburg FA, Giovanella L, Hoffmann M, Iakovou I, Mihailovic J, Ovcaricek PP, et al. New! F-18-based PET/CT for sodium-iodine-symporter-targeted imaging! Eur J Nucl Med Mol Imaging. 2020;47(11):2484–6. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20. Guo R, Xi Y, Zhang M, Miao Y, Zhang M, Li B. Human sodium iodide transporter gene-mediated imaging and therapy of mouse glioma, comparison between (188)Re and (131)I. Oncol Lett. 2018;15(3):3911–7. Cho JY, Shen DH, Yang W, Williams B, Buckwalter TL, La Perle KM, et al. In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas. Gene Ther. 2002;9(17):1139–45. Opyrchal M, Allen C, Iankov I, Aderca I, Schroeder M, Sarkaria J, et al. Effective radiovirotherapy for malignant gliomas by using oncolytic measles virus strains encoding the sodium iodide symporter (MV-NIS). Hum Gene Ther. 2012;23(4):419–27. Spellerberg R, Benli-Hoppe T, Kitzberger C, Berger S, Schmohl KA, Schwenk N, et al. Selective sodium iodide symporter (NIS) gene therapy of glioblastoma mediated by EGFR-targeted lipopolyplexes. Mol Ther Oncolytics. 2021;23:432–46. Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013;368(7):623–32. Jentzen W, Hoppenbrouwers J, van Leeuwen P, van der Velden D, van de Kolk R, Poeppel TD, et al. Assessment of lesion response in the initial radioiodine treatment of differentiated thyroid cancer using 124I PET imaging. J Nucl Med. 2014;55(11):1759–65. Castillo-Rivera F, Ondo-Mendez A, Guglielmi J, Guigonis JM, Jing L, Lindenthal S, et al. Tumor microenvironment affects exogenous sodium/iodide symporter expression. Transl Oncol. 2021;14(1):100937.