Dual-targeted 68 Ga-NOTA-3P-TATE-RGD PET/CT in Radioactive-iodine Negative Differentiated Thyroid Cancer : An Exploratory Comparative Study With 18 F-FDG.

Abstract

This exploratory study aimed to evaluate the clinical feasibility and added diagnostic value of the heterodimeric agent 68 Ga-NOTA-3P-TATE-RGD, targeting both SSTR2 and integrin α v β 3 , in patients with radioactive-iodine-negative differentiated thyroid cancer (DTC), through a comparison with 18 F-FDG PET/CT. Twenty-two patients with radioactive-iodine-negative DTC underwent both 68 Ga-NOTA-3P-TATE-RGD and 18 F-FDG PET/CT within 1 week. Diagnostic performance and semiquantitative parameters were compared between the two agents. Based on the collected gene mutation data, a preliminary analysis was conducted on differences in PET uptake among different gene mutation types. A total of 265 and 295 lesions were detected on 68 Ga-NOTA-3P-TATE-RGD and 18 F-FDG PET/CT, respectively. 68 Ga-NOTA-3P-TATE-RGD detected 45 exclusive lesions (12.71%), predominantly in bone (6 lesions) and brain (5 lesions), while 18 F-FDG identified 75 exclusive lesions in lymph nodes (24 lesions) and lungs (51 lesions). The dual-targeted agent exhibited superior total specificity (92.3% vs 70.6%) and significantly higher tumor-background ratio for bone metastases [3.4 (2.6, 4.0) vs 2.3 (1.6, 2.9), P = 0.008]. For PET comparison of different gene mutations, 68 Ga-NOTA-3P-TATE-RGD showed highest uptake in TERT promoter-mutant lesions ( P < 0.01), while 18 F-FDG had maximal uptake in BRAF-mutant lesions ( P < 0.01). 68 Ga-NOTA-3P-TATE-RGD PET/CT is feasible for radioactive-iodine-negative DTC, providing complementary diagnostic information to 18 F-FDG with enhanced detection of bone and brain metastases. The intense uptake observed in lesions with TERT-associated aggressive subtypes supports potential utility for specific disease identification.