Thyroid cancer, divided in the subvarieties of papillary and follicular carcinoma, together also called differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC), is the most common endocrine malignancy. Over the course of the last seven decades multiple molecular nuclear therapies have been tried to treat the various varieties of thyroid cancer. The sodium iodine symporter (NIS) substrate I-131 is a well known and extremely successful agent to treat DTC, but is not successful in treating other thyroid cancer varieties and some de-differentiated DTC tumors. An alternative to I-131 are radioactively labeled somatostatin analogues, which have predominantly been used to target MTC, but may also be effective in some DTC cases. In experimental preclinical studies the re-induction of NIS expression or transfection with recombinant NIS shows some promise for the treatment of ATC and dedifferentiated DTC. Furthermore, several other potential radioactive NIS substrates are developed. In this review, we will extensively discuss the aforementioned established therapeutic modalities and promising new concepts in molecular nuclear therapy of thyroid carcinoma.
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