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A spotlight on redifferentiation strategies and target modulation in differentiated thyroid cancer

Radioactive iodine (RAI) is a cornerstone for metastatic thyroid cancer treatment since the 40 s and the frst real example of a theragnostic approach in Nuclear Medicine. The most important paradigm of the theragnostic approach is related to the possibility to identify by in vivo imaging the expression of a therapeutic target(s) as well as prognostic factors infuencing patients’ outcomes. In thyroid cancer, the target is the sodium–iodine symporter (NIS), whose expression on cell surface and functionality varies in diferent cancers. For the in vivo evaluation of NIS expression and subsequent NIS- targeted therapy several iodine isotopes can help us in obtaining diagnostic and dosimetric information (123I ; 124I ; 131I) and treating thyroid cancer patients (131I) [1]. A further step of the theragnostic approach is the possibility to pharmacologically manipulate target(s) expression to improve radionuclide therapy efcacy. In this feld, thyroid cancer is again the frst example of the feasibility of target(s) manipulation before 131I therapy to reinduce tumor diferentiation. This paper has the principal aim to give a spotlight on principles and the available results of clinical trials focused on rediferentiation strategies in thyroid cancer, to share with the scientifc community the need to implement research in this feld as possible very promising direction for radionuclide therapy and to underline still open questions/perspectives for the future.

redifferentiation ; thyroid cancer ; radioiodine therapy

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