Modern Diagnostic and Therapeutic Approaches in Thyroid Diseases: Theranostics and the Changing Role of Radioactive Isotopes

Abstract

Radioactive iodine was the first isotope engaged in a theranostic approach, initially used to treat thyroid diseases. The first radioiodine treatments were done in the early 1940s. Based on the high effectivity of the sodium iodine transporter, highly specific uptake and striking effects could be achieved with radioiodine therapy. Initially, I-128 was used, it was substituted by I-130 and finally I-131 with respect to superior physical and logistic issues. It took several decades and successes in radiochemistry to produce the observed convincing effects similar to radioiodine treatment in the therapy of other diseases, particularly in malignancies. The classic theranostic feature of I-131 with beta- and gamma-radiation can still be addressed as a blueprint for modern treatment regimens with radioactive isotopes. Nevertheless, the “classic” indications for radioiodine treatments are decreasing, particularly in low-risk differentiated thyroid cancer. Several tracers were developed to visualize iodine-negative tissue for PET as well as for SPECT imaging for therapy planning and response assessment. Substances like dabrafenib proved to be able to reinduce radioiodine uptake in some patients (depending on, e.g., BRAF positivity), and also theranostics established in other oncological settings showed tumoricide effects in thyroid cancer, e.g., Lu-177-DOTATATE. Other theranostic substances “in the pipeline” like FAPI are candidates for the treatment of thyroid cancer as well.