*3.2. αvβ3 Integrin-Targeting Probes*

The integrin αvβ3 expression on epithelial cells and mature endothelial cells is relatively low, however, it is commonly and highly expressed in solid tumors. RGD and RGD2 are peptides that bind integrin αvβ3 [84]. Recently, the dimeric [68Ga]Ga-DOTA-RGD2 has been successfully applied for PET imaging of RR-DTCs in clinical settings [85], showing sensitivity, specificity, and accuracy of 82.3%, 100%, and 86.4%, respectively, which exceeds the same measurements in [18F]FDG of 82.3%, 50%, and 75%, respectively. For RR-DTCs, the advantage provided by [68Ga]Ga-DOTA-RGD2 is the ability to detect lesions not detected by [18F]FDG [85] (Figure 5). Furthermore, diagnosis of RR-DTCs using [68Ga]Ga-DOTA-RGD2 is better accompanied by [177Lu]Lu-DOTA-RGD2, a potential treatment option for RR-DTCs [86]. Considering that [68Ga]Ga-DOTA-RGD2 and [177Lu]Lu-DOTA-RGD2 are a useful theranostic pair for RR-DTCs, the potential to improve the theranostic landscape of RR-DTCs by sequentially using these agents is high. Nuclear medicine approaches have revolutionized the theranostic arsenal for DTCs, and we are confident that there is room to optimize the management of RR-DTCs with these novel agents.
