Differentiated Thyroid Cancer (DTC) is a well-established model of the theranostic concept, combining functional diagnosis and targeted therapy through the use of Iodine-131. Population-based studies indicate that thyroid cancer incidence has steadily increased and is projected to rise until 2040 (GLOBOCAN), showing its clinical relevance. Despite high survival rates, DTC biological heterogeneity has revealed important limitations in the uniform application of radioiodine therapy, predominantly affecting tumors with partial dedifferentiation, aggressive behavior, or refractoriness to the use of Iodine-131. Advances in hybrid imaging, molecular biology, and risk stratification emphasize the need for translational approaches integrating clinical, functional, and molecular data to improve diagnostic accuracy and therapeutic precision. This study aims to critically analyze the contemporary literature on the use of Iodine-131 in the theranostic approach to DTC, focusing on diagnostic advances, predictors of therapeutic response, mechanisms of radioiodine resistance, and translational research challenges. A systematic search was conducted in PubMed, MEDLINE, and SciELO databases using the keywords: “Theranostics”; “Thyroid Neoplasms”; “Radioactive Iodine”; “Combined Modality Therapy”; “Differentiated Carcinoma”. A total of 25 articles written in English, Portuguese, and Spanish published between 2015 and 2024 were included. Results: The present study shows that integrating hybrid imaging techniques with molecular and clinical parameters enhances diagnostic accuracy, disease extent evaluation, and risk stratification. Findings demonstrate that genetic alterations, NIS expression, and tumor phenotypic characteristics directly influence Iodine-131 uptake. Personalized strategies, including patient selection, tumor redifferentiation and dose modulation, show promise, though methodological and translational limitations persist. Iodine-131 theranostics remains central in DTC management, representing an oncology paradigm. Tumor NIS expression levels are strongly associated with Iodine-131 absorption, suggesting its potential as a biomarker for patient selection. Additionally, pharmacological redifferentiation strategies, such as MAPK pathway inhibition, have shown promise in restoring radioiodine sensitivity in refractory tumors, highlighting actionable translational approaches. In this regard, the integration of hybrid imaging with molecular profiling was shown to improve staging accuracy, disease extent evaluation, and risk stratification, enabling more precise therapies. Nevertheless, the present abstract emphasizes the maintenance of significant barriers to clinical implementation such as methodological heterogeneity, small sample sizes, and lack of standardized protocols. Therefore, strengthening translational research is essential to optimize patient selection, treatment strategies, and enhance the clinical benefits of I-131 in an increasingly complex oncological scenario.
Huada et al. (Sun,) studied this question.