SVCT2-targeted PET imaging agent for the evaluation of LN metastasis of thyroid cancer

Cervical lymph node (LN) metastasis is highly prevalent in thyroid cancer (TC). However, the lack of diagnostic modalities that enable real-time assessment of LN metastasis remains a challenge in providing efficient clinical decision-making and optimal patient care. Sodium-ascorbate co-transporters (SVCTs) have shown high expression levels in TC, presenting a potential target for visualizing LN metastasis. In this study, we successfully prepared [¹⁸F]FAA, targeting SVCT2, with high radiochemical yield. Subsequently, we demonstrated a significantly high expression of SVCT2 in LN metastasis compared to normal tissues. Then, we demonstrated that [¹⁸F]FAA exhibited a significant and specific uptake in TC cells expressing SVCT2. Biodistribution and micro-PET/CT imaging in tumor and lymphadenitis model mice indicated significant [¹⁸F]FAA uptake in tumors but not in regions of LN inflammation. Preliminary clinical investigations revealed that [¹⁸F]FAA detected a greater number of LN metastatic lesions with higher mean SUVmax and tumor-to-background ratio (TBR) than [¹⁸F]FDG. These results highlight the potential of [¹⁸F]FAA as a non-invasive imaging agent for accurately detecting LN metastasis in TC.