*2.1. Sodium Iodine Symporter (NIS)-Targeting Probes*

NIS is the protein mainly locating at the cell plasma membrane, which carries Na+/Iions from the extracellular matrix into the intracellular fluid [23]. The transported iodine, as an element, helps produce thyroid hormone (iodide organification) [24]. Unlike the expression pattern of other tumor targets (low expression in normal tissues and high expression in tumor tissues), NIS is usually present at high levels in normal thyroid tissues and DTC cells, enabling radioiodine collection in normal thyroid and TC cells [25]. Nevertheless, NIS downregulation happens in RR-DTCs, poorly differentiated TCs (PDTCs), and ATCs, causing these TC cells hard to benefit much from radioiodine treatment [26].
