Molecular Imaging and Theragnostics of Thyroid Cancers

Abstract

Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., ¹³¹I, ¹²³I, ¹²⁴I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [¹⁸F]F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [¹⁸F]F-dihydroxyphenylalanine (6-[¹⁸F]FDOPA) PET/CT and/or [¹⁸F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review.

Keywords: molecular imaging; positron emission tomography; radioiodine; theragnostics; thyroid cancer.

Figure 1

(A,B) 40 years old female, with multifocal papillary microcarcinoma (left lobe 7 mm and 2 foci of 1 mm in the right lobe (pT1a(m)N0). TSH 67.83 mIU/L, Tg 11.83 μg/L (<2 μg/L), and TgA 2.2 kIU/L (<4.5 kIU/L). Diagnostic WBS and SPECT/CT (A,B) performed after application of 74 MBq of [¹³¹I] show two focuses of [¹³¹I] uptake—larger in the right upper part of the region VI and small focus lower in the region VI, right paratracheal. The patient was treated with 1665 MBq (45 mCi) of [¹³¹I]. Post-treatment [¹³¹I] WBS (C) shows an accumulation of the [¹³¹I] in the same two focuses.

Figure 2

Post-treatment high-activity ¹³¹I whole-body scintigraphy. Large thyroid remnant with a small single iodine-avid lymph node metastasis (red arrows) at central neck compartment.

Figure 3

Post-treatment high-activity ¹³¹I whole-body scintigraphy. Multiple cervical and mediastinal iodine-avid metastatic lymph nodes and diffuse lung “miliariform” metastases.

Figure 4

DTC patient with increasing thyroglobulin and negative diagnostic whole-body scan after thyroidectomy and radioiodine therapy. [¹⁸F]FDG-avid relapsing disease.

Figure 5

Advanced radioiodine-refractory and [¹⁸F]FDG-avid metastatic thyroid carcinoma involving the thyroid “in toto” with multiple metastases (lymph nodes, lung, liver, kidney, and bone).

Figure 6

[¹⁸F]FDG-PET/CT: anaplastic thyroid cancer with diffuse loco-regional invasion, lymph node, and distant metastases (lung, heart, and bone).

Figure 7

Bifocal and bilateral medullary thyroid carcinoma. Pre-operative PET/CT: primary tumors positive at [¹⁸F]FDOPA (top) and [¹⁸F]F-SiFAlinTATE (bottom).

Figure 8

Bifocal and bilateral medullary thyroid carcinoma. Preoperative PET/CT: arrows showing bilateral lymph node metastases negative at [¹⁸F]FDOPA (top) and positive at [¹⁸F]F-SiFAlinTATE (bottom).