¹⁸F-fluorodeoxyglucose positron emission tomography combined with computed tomography for the prediction of radioiodine therapy response in patients with metastatic differentiated thyroid cancer

The study objective was to investigate the role of ¹⁸ F-fluorodeoxyglucose (¹⁸ F-FDG) positron emission tomography combined with computed tomography (PET-CT) as an indirect determination of the differentiation status of metastases and for the prediction of radioactive iodine (RAI) therapy response in patients with metastatic differentiated thyroid cancer.
Materials and methods. The 40 metastatic differentiated thyroid cancer patients were enrolled in the study that underwent both post-therapeutic radioiodine scan and PET-CT at the same period.
Results. The study found that 12 (30 %) patients responded to RAI therapy. The remaining 28 (70 %) patients not responded to RAI therapy showed stabilization or progression. The accumulation of radioiodine by metastases positively correlated with the total response rate, while the ¹⁸ F-FDG avidity is negative. Significant direct correlation with response rate was observed in the group with only radioiodine uptake. However, this correlation was not observed in the patients with both tracers uptake. The patients with ¹⁸ F-FDG-positive metastases showed poor response to RAI therapy, regardless of the degree of radioiodine uptake.
Conclusion. The ¹⁸ F-FDG uptake by metastases is a predictor of a poor response to RAI therapy, even in the presence of RAI uptake. The use of ¹⁸ F-FDG PET-CT in patients with metastatic differentiated thyroid cancer can be recommended at the beginning of RAI therapy to clarify the prognosis and provide a personalized approach to the treatment and observation of the most difficult category of patients.

1. Hong C.M., Lee W.K., Jeong S.Y. et al. Superiority of delayed risk stratification in differentiated thyroid cancer after total thyroidectomy and radioactive iodine ablation. Nucl Med Commun 2014;35(11):1119–26. DOI: 10.1097/MNM.0000000000000183.

2. Sampson E., Brierley J.D., Le L.W. et al. Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis. Cancer 2007;110(7):1451–6. DOI: 10.1002/cncr.22956.

3. O’Neill C.J., Oucharek J., Learoyd D., Sidhu S.B. Standard and emerging therapies for metastatic differentiated thyroid cancer. Oncologist 2010;15(2):146–56. DOI: 10.1634/theoncologist.2009-0190.

4. Verburg F.A., Hanscheid H., Luster M. Radioactive iodine (RAI) therapy for metastatic differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab 2017;31(3):279–90. DOI: 10.1016/j.beem.2017.04.010.

5. Chung J.-K., Cheon G.J. Radioiodine therapy in differentiated thyroid cancer: the first targeted therapy in oncology. Endocrinol Metab (Seul) 2014;29(3):233–9. DOI: 10.3803/EnM.2014.29.3.233.

6. Haugen B.R., Alexander E.K., Bible K.C. et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26(1):1–133. DOI: 10.1089/thy.2015.0020.

7. Pacini F., Ito Y., Luster M. et al. Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Rev Endocrinol Metab 2012;7(5):541–54. DOI: 10.1586/eem.12.36.

8. Schlumberger M., Brose M., Elisei R. et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol 2014;2(5):356–8. DOI: 10.1016/s2213-8587(13)70215-8.

9. Durante C., Haddy N., Baudin E. et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 2006;91(8):2892–9. DOI: 10.1210/jc.2005-2838.

10. Maxon H.R., Thomas S.R., Hertzberg V.S. et al. Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med 1983;309(16):937–41. DOI: 10.1056/NEJM198310203091601.

11. Castro M.R., Bergert E.R., Goellner J.R. et al. Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake. J Clin Endocrinol Metab 2001;86(11):5627–32. DOI: 10.1210/jcem.86.11.8048.

12. Kang S.Y., Bang J.-I., Kang K.W. et al. FDG PET/CT for the early prediction of RAI therapy response in patients with metastatic differentiated thyroid carcinoma. PLoS One 2019;14(6):e0218416. DOI: 10.1371/journal.pone.0218416.

13. Feine U., Lietzenmayer R., Hanke J.P. et al. [18 FDG whole-body PET in differentiated thyroid carcinoma. Flip-flop in uptake patterns of18 FDG and131 I (In German)]. Nuklearmedizin 1995;34(4):127–34.

14. Duarte P.S., Marin J.F.G., de Carvalho J.W.A. et al. Iodine/FDG “flip-flop” phenomenon inside a large metastatic thyroid cancer lesion better characterized on SPECT/CT and PET/CT studies. Clin Nucl Med 2018;43(6):436–8. DOI: 10.1097/RLU.0000000000002046.

15. Pace L., Klain M., Salvatore B. et al. Prognostic role of18 F-FDG PET/CT in the postoperative evaluation of differentiated thyroid cancer patients. Clin Nucl Med 2015;40(2):111–5. DOI: 10.1097/RLU.0000000000000621.

16. Min J.J., Chung J.K., Lee Y.J. et al. Relationship between expression of the sodium/iodide symporter and131 I uptake in recurrent lesions of differentiated thyroid carcinoma. Eur J Nucl Med 2001;28(5):639–45.

17. Chung J.K. Sodium iodide symporter: its role in nuclear medicine. J Nucl Med 2002;43(9):1188–200.

18. Moon S.H., Oh Y.L., Choi J.Y. et al. Comparison of18 F-fluorodeoxyglucose uptake with the expressions of glucose transporter type 1 and Na+ /I – symporter in patients with untreated papillary thyroid carcinoma. Endocr Res 2013;38(2):77–84. DOI: 10.3109/07435800.2012.713426.

19. Kim S., Chung J.K., Min H.S. et al. Expression patterns of glucose transporter-1 gene and thyroid specific genes in human papillary thyroid carcinoma. Nucl Med Mol Imaging 2014;48(2):91–7. DOI: 10.1007/s13139-013-0249-x.

20. Deandreis D., Al Ghuzlan A., Leboulleux S. et al. Do histological, immunohistochemical and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome? Endocr Relat Cancer 2011;18(1):159–69. DOI: 10.1677/ERC-10-0233.

21. Rivera M., Ghossein R.A., Schoder H. et al. Histopathologic characterization of radioactive iodine-refractory fluorodeoxyglucose positron emission tomography-positive thyroid carcinoma. Cancer 2008;113(1):48–56. DOI: 10.1002/cncr.23515.

22. Liu M., Cheng L., Jin Y. et al. Predicting 131 I-avidity of metastases from differentiated thyroid cancer using 18 F-FDG PET/CT in postoperative patients with elevated thyroglobulin. Sci Rep 2018;8(1):4352. DOI: 10.1038/s41598-018-22656-4.