Cover
Vol. 3 No. 2 (2025)

Published: December 1, 2025

Pages: 31-42

Original Article

From Diagnosis to Therapy: A Comprehensive Review on the Role of Radioactive Isotopes in Thyroid Cancer Management

Zahraa A. Rasheed 1 Hawraa K. Ayyed Zeena J. Raheem Tebarak A.A. Al-Salmani 2
1Department of Physics, College of Education, Al-Iraqia University, Baghdad, IRAQ.
2Department of Medical Physics, College of Applied Science, University of Fallujah, Fallujah, IRAQ.
History
  • Received: September 27, 2025
  • Accepted: November 10, 2025
  • Available Online: December 1, 2025

Abstract

The use of radioactive isotopes in the diagnosis and treatment of thyroid cancer is now an integral part of modern nuclear medicine. Gamma-emitting isotopes such as technetium-99m and iodine-123 serve as the main diagnostic imaging weapon enabling great sensitivity and specificity, non-invasive functional visualization of thyroid physiology and disease. Todine-131 is the dominant therapeutic isotope, emitting cytotoxic beta radiation for the treatment of metastatic differentiated thyroid cancer and thyroid remnant ablation. The effectiveness of radioactive iodine treatment is dependent on various factors including sodium-iodide symporter expression as well as dosimetry methods seeking to maximize absorbed dosages whilst simultaneously achieving successful treatment alongside minimizing non-target organ toxicity. Molecular radiotheragnostics and personalized dosimetry methods are slowly entering the clinical routine and will ensure higher diagnostic power and treatment efficacy in the future. Radioiodine-refractory thyroid cancers have long been challenging to manage, warranting novel approaches to integrate molecular biology, targeted therapies and immunotherapy. The changing context of radionuclide use in thyroid care highlights the necessity of multidisciplinary approaches, which promise to increase patient outcomes and the management of thyroid cancer

Keywords

References

  1. McCready R, Gnanasegaran G, Bomanji JB. A history of radionuclide studies in the UK: 50th anniversary of the British Nuclear Medicine Society. 2016: 9-18. https://doi.org/10.1007/978-3-319-28624-2
  2. Zhang S, Wang X, Gao X, Chen X, Li L, Li G, Liu C, Miao Y, Wang R, Hu K. Radiopharmaceuticals and their applications in medicine. Sig Transduct Target Ther. 2025;10(1):1-51. https://doi.org/10.1038/s41392-024-02041-6
  3. Ehrhardt JD Jr, Güleç S. A review of the history of radioactive iodine theranostics: the origin of nuclear ontology. Mol Imaging Radionucl Ther. 2020;29(3):88-97. https://doi.org/10.4274/mirt.galenos.2020.83703
  4. Royal L. Radioactive Tracers for Medical Diagnostics: A Nuclear Medicine Perspective. J Nucl Med Radiat Ther. 2024;15(1):1-2.
  5. Sharma R, Aboagye E. Development of radiotracers for oncology–the interface with pharmacology. Br J Pharmacol. 2011;163(8):1565-85. https://doi.org/10.1111/j.1476-5381.2010.01160.x
  6. Fahey FH, Alison BA, Treves ST, Grant FD. Nuclear medicine and radiation protection. J Radiol Nurs. 2016;35(1):5-11. https://doi.org/10.1016/j.jradnu.2015.12.005
  7. International Atomic Energy Agency. Radiotracer Applications in Industry: A Guidebook. 2004.
  8. Thiagarajan B. Anatomy of thyroid gland: Surgeon's perspective. Online J Otolaryngol. 2015;5.
  9. Arrangoiz R, Cordera F, Caba D, Muñoz M, Moreno E, de León EL. Comprehensive review of thyroid embryology, anatomy, histology, and physiology for surgeons. Int J Otorhinolaryngol Head Neck Surg. 2018;7(4):160-88.
  10. Benvenga S, Tuccari G, Ieni A, Vita R. Thyroid gland: anatomy and physiology. Encyclopedia of Endocrine Diseases. 2018;4:382-90.
  11. Romitti M, Costagliola S. Progress toward and challenges remaining for thyroid tissue regeneration. Endocrinol. 2023;164(10):bqad136.
  12. Nilsson M, Fagman H. Development of the thyroid gland. Development. 2017;144(12):2123-40.
  13. Beynon ME, Pinneri K. An overview of the thyroid gland and thyroid-related deaths for the forensic pathologist. Acad Forensic Pathol. 2016;6(2):217-36.
  14. Brent GA, Mestman JH. Physiology and Tests of Thyroid Function. 2008.
  15. Shahid MA, Ashraf MA, Sharma S. Physiology, thyroid hormone. 2018.
  16. Sorrenti S, Baldini E, Pironi D, Lauro A, D’Orazi V, Tartaglia F, Ulisse S. Iodine: Its role in thyroid hormone biosynthesis and beyond. Nutrients. 2021;13(12):382-90.
  17. Gunnarsdóttir I, Brantsæter AL. Iodine: a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res. 2023;67(10369):1-10. https://doi.org/10.29219/fnr.v67.10369
  18. Smyth PP. Narrative review: iodine—thyroidal and extrathyroidal actions. Ann Thyroid. 2022;7(4):1-12. https://doi.org/10.21037/aot-21-28
  19. Gong B, Wang X, Wang C, Yang W, Shan Z, Lai Y. Iodine-induced thyroid dysfunction: a scientometric study and visualization analysis. Front Endocrinol. 2023;1-12. https://doi.org/10.3389/fendo.2023.1239038
  20. Khudair A, Khudair A, Niinuma SA, Habib H, Butler AE. From deficiency to excess: the impact of iodine excess on reproductive health. Front Endocrinol. 2025;16:1-8. https://doi.org/10.3389/fendo.2025.1568059
  21. Andersson M, Braegger CP. The role of iodine for thyroid function in lactating women and infants. Endocr Rev. 2022;43(3):469-506. https://doi.org/10.1210/endrev/bnab029
  22. Taprogge J, Gape PM, Carnegie-Peake L, Murray I, Gear JI, Leek F, Flux GD. A systematic review and meta-analysis of the relationship between the radiation absorbed dose to the thyroid and response in patients treated with radioiodine for graves' disease. Thyroid. 2021;31(12):1829-38. https://doi.org/10.1089/thy.2021.0302
  23. Hong CM, Ahn BC. Factors associated with dose determination of radioactive iodine therapy for differentiated thyroid cancer. Nucl Med Mol Imaging. 2018;52(4):247-53. https://doi.org/10.1007/s13139-018-0522-0
  24. Saenko V, Mitsutake N. Radiation-related thyroid cancer. Endocr Rev. 2024;45(1):1-29. https://doi.org/10.1210/endrev/bnad022
  25. Manzil FFP, Kaur H. Radioactive Iodine Therapy for Thyroid Malignancies. 2024;1-12.
  26. Mohammed SI. The Use of Technetium-99m Radioactive Isotope in The Diagnosis and Treatment of Thyroid Diseases: A Review. Al-Kitab J Pure Sci. 2025;9(01):51-67. https://doi.org/10.32441/kjps.09.01.p4
  27. Oh SW, Park S, Chong A, Kim K, Bang JI, Seo Y, Lee SW. Nuclear Medicine Imaging in Differentiated Thyroid Cancer: Summary of the Korean Thyroid Association Guidelines 2024 from Nuclear Medicine Perspective, Part-I. Nucl Med Mol Imaging. 2025;59(1):1-7. https://doi.org/10.1007/s13139-024-00885-y
  28. Yavuz S, Puckett Y. Iodine-131 uptake study. 2023;1-6.
  29. Gholami A, Armaghan N, Shirafkan H, Amiri M, Anijdan SHM. Normal reference values for Tc-99m pertechnetate thyroid uptake in northern Iranian population: A single-center experience. Casp J Intern Med. 2024;15(3):459-65. https://doi.org/10.22088/cjim.15.3.459
  30. Iqbal A, Rehman A. Thyroid uptake and scan. 2022;1-4.
  31. Jaiswal G, Grimes M, Bononi P, Vaghasia N, Khan S, Andre K, Alkhaddo J. Usefulness of Preradioactive Iodine Scans in Thyroid Cancer. J Endocr Soc. 2025;9(9):1-5. https://doi.org/10.1210/jendso/bvaf128
  32. Meier DA, Kaplan MM. Radioiodine uptake and thyroid scintiscanning. Endocrinol Metab Clin N Am. 2001;30(2):291-313. https://doi.org/10.1016/S0889-8529(05)70188-2
  33. Lechner MG, Brent GA. A new twist on a classic: enhancing radioiodine uptake in advanced thyroid cancer. Clin Cancer Res. 2024;30(7):1220-2. https://doi.org/10.1158/1078-0432.CCR-23-3503
  34. Chaudhary V, Bano S. Imaging of the thyroid: Recent advances. Indian J Endocrinol Metab. 2012;16(3):371-6. https://doi.org/10.4103/2230-8210.95674
  35. Reading CC, Gorman CA. Thyroid imaging techniques. Clin Lab Med. 1993;13(3):711-24. https://doi.org/10.1016/S0272-2712(18)30435-9
  36. Giovanella L, Avram AM, Ovčariček PP, Clerc J. Thyroid functional and molecular imaging. Presse Med. 2022;51(2):1-18. https://doi.org/10.1016/j.lpm.2022.104116
  37. Lee YH, Baek JH, Jung SL, Kwak JY, Kim JH, Shin JH. Ultrasound-guided fine needle aspiration of thyroid nodules: a consensus statement by the Korean Society of Thyroid Radiology. Korean J Radiol. 2015;16(2):391-401. https://doi.org/10.3348/kjr.2015.16.2.391
  38. Liu Q, Ouyang L, Zhang S, Yang Y. Comparison of the value of ultrasound-guided fine needle aspiration biopsy and contrast-enhanced ultrasound in different sizes of thyroid nodules. Medicine. 2024;103(39):1-7. https://doi.org/10.1097/MD.0000000000039843
  39. Bahrami A, Valizadeh S, Aghamohammadzadeh N, Najafipour F, Halimi M, Javad-Rashid R, Houshyar J. Consistency analysis of ultrasound-guided fine-needle aspiration and histopathology results in thyroid nodules. Immunopathol Persa. 2022;28(1):1-7. https://doi.org/10.34172/ipp.2022.31350
  40. Indra B, Qodir N, Pramudhito D, Legiran L, Hafy Z, Yusran AMI. Effectiveness of radioiodine therapy on preventing recurrence in differentiated thyroid carcinoma: a systematic review. J Egypt Natl Canc Inst. 2025;37(1):1-11. https://doi.org/10.1186/s43046-025-00293-z
  41. Sapienza MT, Willegaignon J. Radionuclide therapy: current status and prospects for internal dosimetry in individualized therapeutic planning. Clinics. 2019;74:1-8. https://doi.org/10.6061/clinics/2019/e835
  42. Gómez-Sáez JM. Current and future perspectives in thyroid carcinoma treatment. Eur Endocrinol. 2013;9(1):22-7. https://doi.org/10.17925/EE.2013.09.01.22
  43. Guo M, Sun Y, Wei Y, Xu J, Zhang C. Advances in targeted therapy and biomarker research in thyroid cancer. Front Endocrinol. 2024;15:1-16. https://doi.org/10.3389/fendo.2024.1372553
  44. Lepareur N, Ramée B, Mougin-Degraef M, Bourgeois M. Clinical advances and perspectives in targeted radionuclide therapy. Pharmaceutics. 2023;15(6):1-36. https://doi.org/10.3390/pharmaceutics15061733
  45. Shah HJ, Ruppell E, Bokhari R, Aland P, Lele VR, Ge C, McIntosh LJ. Current and upcoming radionuclide therapies in the direction of precision oncology: A narrative review. Eur J Radiol Open. 2023;10:1-19. https://doi.org/10.1016/j.ejro.2023.100477