Chonnam Med J.  2019 Sep;55(3):127-135. 10.4068/cmj.2019.55.3.127.

Identification of Radioactive Iodine Refractory Differentiated Thyroid Cancer

Affiliations
  • 1Department of Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing, China. linys@pumch.cn
  • 2Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China.

Abstract

Most differentiated thyroid cancer (DTC) patients have an excellent prognosis. However, about one-third of DTC patients with recurrent or metastatic disease lose the hallmark of specific iodine uptake initially or gradually and acquire radioactive iodine-refractory DTC (RAIR-DTC) with poor prognosis. Due to the potentially severe complications from unnecessarily repeated RAI therapy and encouraging progress of multiple targeted drugs for advanced RAIR-DTC patients, it has become crucial to identify RAIR-DTC early. In this review, we focus on the progress and controversies regarding the defining of RAIR-DTC, further with subsistent approaches and promising molecular nuclear medicine imaging in identifying RAIR-DTC, which may shed light on the proper management methodsof such patients.

Keyword

Thyroid Neoplasms; Iodine Radioisotopes; Molecular Imaging

MeSH Terms

Humans
Iodine Radioisotopes
Iodine*
Molecular Imaging
Nuclear Medicine
Prognosis
Thyroid Gland*
Thyroid Neoplasms*
Iodine
Iodine Radioisotopes

Figure

  • FIG. 1 A 52-year-old man with DTC with negative 131I-WBS and positive 18F-FDG PET/CT. The patient had an elevated serum Tg but negative 131I-WBS. 18F-FDG PET/CT was recommended and displayed two right hilar lymph nodes with metastatic carcinoma. (A) 131I-WBS, (B) PET MIP imaging, (C, F) CT, (D, G) PET, (E, H) fusion.

  • FIG. 2 The mechanism of BRAFV600E mutation negatively regulates sodium iodide symporter (NIS) and Integrin targeted imaging. On the one hand, BRAFV600E mutation promotes NIS silence by histone deacetylation (HDAC) of NIS promoter, on the other hand, BRAFV600E mutation promotes the secretion of transforming growth factor β (TGFβ), which, through the activation of SMADs and consequent impairment of the thyroid-gene transcription factor PAX8. BRAF oncoprotein can activate ERK1/2 signal through mitogen-activated protein kinase (MAPK) pathway, then thrombospondin-1 (TSP-1) was upregulated, TSP-1 further positively regulates the expression of integrin, which in turn increases the level of ERK1/2 signal, forming a positive feedback.

  • FIG. 3 The nuclear imaging for identifying RAIR-DTC. Negative 131I-WBS act as fundamental indicator for RAIR-DTC identifying, while there still are plenty of influencing factors. Other nuclear imaging modalities could be complements with progressed researches. 131I-WBS: 131I-whole-body scan, RAI: radioactive iodine, RAIR-DTC: radioactive iodine refractory differentiated thyroid cancer, FDG: fluorodeoxyglucose, RGD: Arg-Gly-Asp, PSMA: prostate-specific membrane antigen, SSTR: Somatostatin receptors.


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