Theranostic Approaches to Radioiodine-Refractory Differentiated Thyroid Cancer: A Narrative Review
Cancers, vol.18, no.12, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Review
- Volume: 18 Issue: 12
- Publication Date: 2026
- Doi Number: 10.3390/cancers18121937
- Journal Name: Cancers
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, CINAHL, EMBASE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Keywords: nuclear medicine, radioiodine-refractory thyroid cancer, redifferentiation, targeted therapy, theranostics
- Hacettepe University Affiliated: Yes
Abstract
Background: Radioiodine (Na[131I]I) therapy is the cornerstone of systemic treatment for differentiated thyroid cancer (DTC), exploiting sodium–iodide symporter (NIS) expression for durable control. Up to 30–40% of advanced cases develop radioiodine-refractory disease (RAI-R DTC), marked by impaired iodine uptake, aggressive behavior, and poor response to Na[131I]I. Locoregional treatments, multikinase inhibitors (MKIs), and selective targeted agents improve progression-free survival but are not curative and carry cumulative toxicity, motivating precision-based alternatives. The primary objective of this review is to clarify the evolving theranostic paradigm in RAI-R DTC; the secondary objectives are to appraise redifferentiation and iodine-based theranostics for restoring or exploiting iodine avidity and to evaluate non-iodine theranostic strategies for cases where iodine biology is absent, impaired, or unreliable. Methods: This narrative review synthesizes contemporary evidence on theranostic strategies in RAI-R DTC, drawn from available studies, clinical trials, and current guidelines, with an emphasis on redifferentiation and non-iodine approaches; a systematic search protocol was not applied. Results: Theranostics couples target-specific molecular imaging with matched radionuclide therapy and response-adapted sequencing. Its most transformative application is redifferentiation, in which pharmacologic modulation of oncogenic signaling can restore iodine avidity and enable renewed, dosimetry-guided Na[131I]I treatment. Beyond iodine, somatostatin receptor (SSTR) imaging and peptide receptor radionuclide therapy (PRRT) have re-emerged in very selected cases, whereas alpha emitters remain investigational. Refractoriness is increasingly viewed as a reversible continuum rather than a fixed state. Conclusions: Theranostics can individualize RAI-R DTC treatment, restoring or exploiting iodine biology where possible and shifting to non-iodine targets where it is unreliable. Patient selection, timing, and integration with systemic therapy are central, and prospective validation is needed.