Journal of Radioanalytical and Nuclear Chemistry

, Volume 311, Issue 3, pp 1697–1708 | Cite as

Preparation and evaluation of 131I-quercetin as a novel radiotherapy agent against dedifferentiated thyroid cancer

  • Qinghua Xie
  • Xia Li
  • Guanquan Wang
  • Xuan Hou
  • Yujun Wang
  • Hongbo Yu
  • Changfa Qu
  • Shunzhong Luo
  • Yali CuiEmail author
  • Chuanqin XiaEmail author
  • Ruibing WangEmail author


Here we reported the radiolabeling and evaluation of a novel 131I-radiolabeled quercetin for the treatment of dedifferentiated thyroid cancers. The human thyroid cancer cell lines (FTC-133, TT and DRO) experienced much higher uptake of 131I-quercetin as compared to the free 131I. And the proliferation inhibition rate of 131I-quercetin on in vitro DRO cell line was 86.87 ± 7.15%. Biodistribution and SPECT analysis demonstrated that the injected radioactivity mainly accumulated in tumors. The tumor volume in the treatment group was dramatically inhibited in comparison with the control group.


Dedifferentiated thyroid cancer 131I-quercetin Proliferation inhibition Biodistribution Radiopharmaceutical 



This work was financially supported by the National Science and Technology Support Program (2014BAA03B00), the National Fund for Fostering Talents of Basic Science (J1210004), the National Natural Science Foundations of China (81271526), and University of Macau Research Fund (SRG2014-00025-ICMS-QRCM). We also wish to thank the Comprehensive Training Platform of specialized laboratory at College of Chemistry in Sichuan University (Chengdu, China), and the Analytical & Testing Center at Sichuan University (Chengdu, China) for providing analytical equipment. We are also much grateful to Nuclear Medicine Program of West China Medical School, Sichuan University, for providing various cancer cell lines and the SPECT scan.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving mice were in accordance with the ethical standards of Sichuan University and Harbin Medical University. This study was approved by the animal ethics committee of Sichuan University, where the mice were bred and tested.


  1. 1.
    Xing M (2013) Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 13(3):184–199CrossRefGoogle Scholar
  2. 2.
    Nguyen QT, Lee EJ, Huang MG et al (2015) Diagnosis and treatment of patients with thyroid cancer. Am Health Drug Benef 8(1):30–40Google Scholar
  3. 3.
    Zarebczan B, Chen H (2010) Multi-targeted approach in the treatment of thyroid cancer. Minerva Chir 65(1):59–69Google Scholar
  4. 4.
    Sosa JA, Elisei R, Jarzab B et al (2014) Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid Off J Am Thyroid Assoc 24(2):232–240CrossRefGoogle Scholar
  5. 5.
    Regalbuto C, Frasca F, Pellegriti G, Malandrino P et al (2016) Update on thyroid cancer treatment. Future Oncol 8(10):1331–1348CrossRefGoogle Scholar
  6. 6.
    Luster M, Clarke SE, Dietlein M et al (2008) Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imag 35(10):1941–1959CrossRefGoogle Scholar
  7. 7.
    Kang HJ, Youn YK, Hong MK et al (2011) Antiproliferation and redifferentiation in thyroid cancer cell lines by polyphenol phytochemicals. J Korean Med Sci 26(7):893–899CrossRefGoogle Scholar
  8. 8.
    June-Key Chung GJC (2014) Radioiodine therapy in differentiated thyroid cancer: the first targeted therapy in oncology. Endocrinol Metab 29(3):233–239CrossRefGoogle Scholar
  9. 9.
    Antonelli A, Ferri C, Ferrari SM et al (2009) New targeted molecular therapies for dedifferentiated thyroid cancer. J Oncol 2010(1):6Google Scholar
  10. 10.
    Antonelli A, Fallahi P, Ferrari SM et al (2008) Dedifferentiated thyroid cancer: a therapeutic challenge. Biomed Pharmacother 62(8):559–563CrossRefGoogle Scholar
  11. 11.
    Schneider DF, Chen H (2013) New developments in the diagnosis and treatment of thyroid cancer. Ca-Cancer J Clin 63(6):373–394CrossRefGoogle Scholar
  12. 12.
    Gérard A-C, Daumerie C, Mestdagh C et al (2003) Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas. J Clin Endocrinol Metab 88(10):4977–4983CrossRefGoogle Scholar
  13. 13.
    Nordén MM, Larsson F, Tedelind S et al (2007) Down-regulation of the sodium/iodide symporter explains 131I-induced thyroid stunning. Cancer Res 67(15):7512–7517CrossRefGoogle Scholar
  14. 14.
    Oh SW, Moon SH, Park DJ et al (2011) Combined therapy with i-131 and retinoic acid in korean patients with radioiodine-refractory papillary thyroid cancer. Eur J Nucl Med 38(10):1798–1805CrossRefGoogle Scholar
  15. 15.
    Ke CC, Hsieh YJ, Hwu L et al (2011) Evaluation of lentiviral-mediated expression of sodium iodide symporter in anaplastic thyroid cancer and the efficacy of in vivo imaging and therapy. J Oncol 2011:178967CrossRefGoogle Scholar
  16. 16.
    Kim JE, Ahn BC, Hwang MH et al (2011) Combined rna interference of hexokinase ii and (131)i-sodium iodide symporter gene therapy for anaplastic thyroid carcinoma. J Nucl Med 52(11):1756–1763CrossRefGoogle Scholar
  17. 17.
    Brose MS, Nutting CM, Barbara J et al (2014) Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384(9940):319–328CrossRefGoogle Scholar
  18. 18.
    Gibellini L, Pinti M, Nasi M et al (2011) Quercetin and cancer chemoprevention. Evid Based Complement Alternat Med 2011:1–15CrossRefGoogle Scholar
  19. 19.
    Kleemann R, Verschuren L, Morrison M et al (2011) Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 218(1):44–52CrossRefGoogle Scholar
  20. 20.
    Angst E, Park JL, Moro A et al (2013) The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo. Pancreas 42(2):223–229CrossRefGoogle Scholar
  21. 21.
    Duo J, Ying GG, Wang GW et al (2012) Quercetin inhibits human breast cancer cell proliferation and induces, apoptosis via bcl-2 and bax regulation. Molec Med Rep 5(6):1453–1456Google Scholar
  22. 22.
    Jakubowicz-Gil J, Langner E, Bądziul D et al (2013) Apoptosis induction in human glioblastoma multiforme T98G cells upon temozolomide and quercetin treatment. Tumor Biol 34(4):2367–2378CrossRefGoogle Scholar
  23. 23.
    Niu G, Yin S, Xie S et al (2011) Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells. Acta Biochim Biophys Sin 43(1):30–37CrossRefGoogle Scholar
  24. 24.
    Kang HJ, Lee HS, Price JE et al (2011) Polyphenol phytochemicals induced antiproliferation and redifferentiation in thyroid cancer cell lines. J Korean Med Sci 26(7):893–899CrossRefGoogle Scholar
  25. 25.
    Fang MZ, Wang Y, Ai N et al (2003) Tea polyphenol (−)-epigallocatechin-3-gallate inhibits dna methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63(22):7563–7570Google Scholar
  26. 26.
    Ulrich S, Loitsch SM, Rau O et al (2006) Peroxisome proliferator-activated receptor γ as a molecular target of resveratrol-induced modulation of polyamine metabolism. Cancer Res 66(14):7348–7354CrossRefGoogle Scholar
  27. 27.
    Iwanami T (2011) New generation of enantioenriched allylsilanes. Radiother Oncol 104(3):395–400Google Scholar
  28. 28.
    Chen L (2012) Autophagy plays a role in promoting radiosensitivity of glioma stem/progenitor cells by quercetin. J Radiat Res Radiat Process 30(5):297–302Google Scholar
  29. 29.
    Lin C, Yu Y, H-g Zhao et al (2012) Combination of quercetin with radiotherapy enhances tumor radiosensitivity in vitro and in vivo. Radiother Oncol 104(3):395–400CrossRefGoogle Scholar
  30. 30.
    Phani CR, Vinaykumar C, Rao K et al (2010) Quantitative analysis of quercetin in natural sources by RP-HPLC. Int J Res Pharm Biomed Sci 1(1):19–22Google Scholar
  31. 31.
    Verma N, Trehan N (2013) HPLC analysis of methanolic extract of herbs for quercetin content. J Pharmacogn Phytochem 2(1):159–162Google Scholar
  32. 32.
    Jiang F, Chen L, Yang YC et al (2015) CYP3A5 functions as a tumor suppressor in hepatocellular carcinoma by regulating mTORC2/Akt signaling. Cancer Res 75(7):1470–1481CrossRefGoogle Scholar
  33. 33.
    Kim SH, Chung HK, Kang JH et al (2008) Tumor-targeted radionuclide imaging and therapy based on human sodium iodide symporter gene driven by a modified telomerase reverse transcriptase promoter. Hum Gene Ther 19(9):951–957CrossRefGoogle Scholar
  34. 34.
    Park BN, Choe Y, Lee S et al (2001) Synthesis of iodine-123 labeled quercetin and catechin as radical seeking agents. J Label Compd Radiopharm 44(S1):S957–S958CrossRefGoogle Scholar
  35. 35.
    Barolli MG, Pomilio AB (1997) Synthesis of [131-I]-iodinated quercetin. J Label Compd Radiopharm 39(11):927–933CrossRefGoogle Scholar
  36. 36.
    Jin Lee Y, Chung J-K, Hoon Shin J et al (2004) In vitro and in vivo properties of a human anaplastic thyroid carcinoma cell line transfected with the sodium iodide symporter gene. Thyroid 14(11):889–895CrossRefGoogle Scholar
  37. 37.
    Hosseinimehr SJ, Tolmachev V, Stenerlöw B (2011) 125I-labeled quercetin as a novel DNA-targeted radiotracer. Cancer Biother Radiopharm 26(4):469–475CrossRefGoogle Scholar
  38. 38.
    van der Woude H, Alink GM, van Rossum BE et al (2005) Formation of transient covalent protein and DNA adducts by quercetin in cells with and without oxidative enzyme activity. Chem Res Toxicol 18(12):1907–1916CrossRefGoogle Scholar
  39. 39.
    Nifli AP, Theodoropoulos PA, Munier S et al (2007) Quercetin exhibits a specific fluorescence in cellular milieu: a valuable tool for the study of its intracellular distribution. J Agric Food Chem 55(8):2873–2878CrossRefGoogle Scholar
  40. 40.
    Yasui LS, Chen K, Wang K et al (2007) Using Hoechst 33342 to target radioactivity to the cell nucleus. Radiat Res 167(2):167–175CrossRefGoogle Scholar
  41. 41.
    Lobachevsky PN, White J, Leung M et al (2008) Plasmid breakage by (125)I-labelled DNA ligands: effect of DNA-iodine atom distance on breakage efficiency. Int J Radiat Biol 84(12):991–1000CrossRefGoogle Scholar
  42. 42.
    Walle T, Walle UK, Halushka PV (2001) Carbon dioxide is the major metabolite of quercetin in humans. J Nutr 131(10):2648–2652Google Scholar
  43. 43.
    Li CC, Chi JL, Ma Y et al (2014) Interventional therapy for human breast cancer in nude mice with 131I gelatin microspheres ((1)(3)(1)I-GMSs) following intratumoral injection. Radiat Oncol 9:144CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2016

Authors and Affiliations

  1. 1.College of ChemistrySichuan UniversityChengduChina
  2. 2.College of MathematicsSichuan UniversityChengduChina
  3. 3.Institute of Nuclear Physics and ChemistryChina Academy of Engineering PhysicsMianyangChina
  4. 4.Department of Nuclear MedicineHarbin Medical University Cancer HospitalHarbinChina
  5. 5.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical SciencesUniversity of MacauTaipa, MacauChina

Personalised recommendations