Trop2-Targeted [ 18 F]AlF-RESCA-RT4 ImmunoPET/CT in Guiding Clinical Surgeries of Thyroid Cancers: A Proof-of-Concept Study

Current imaging techniques (ultrasonography, CT) have limited sensitivity for detecting occult lymph node metastases in thyroid cancers. This first-in-human study assesses Trop2-targeted immunoPET/CT for preoperative differentiation of benign and malignant thyroid nodules and for identifying lymph node metastases to aid surgical planning. Sixteen patients with thyroid cancer underwent preoperative Trop2-targeted immunoPET/CT imaging. Tracer uptake (SUVmax) in tumors and lymph nodes was measured, pathology was confirmed through histopathology, and Trop2 expression was validated by immunohistochemistry. Malignant thyroid cancers had higher Trop2 tracer uptake than benign (38.46 ± 8.04 vs 8.97 ± 4.80, P = 0.046), and PTC had a 6.2-fold increase over adjacent normal tissue (46.65 ± 7.54 vs 7.53 ± 1.71, P = 0.007). The uptake value of the Trop2 tracer was strongly correlated to PTC tumor size (Spearman correlation coefficient ρ = 0.81, R 2 = 0.66). Trop2 immunoPET/CT effectively differentiates metastatic lymph nodes (LN (+): 25.15 ± 5.16 vs LN (−): 3.34 ± 1.27, P = 0.00017), with an AUC of 0.89 (95% CI: 0.78–1.00). Diagnosis of lymph node metastasis achieved an accuracy of 91.3%. Both metastatic lymph nodes and PTC show high Trop2 tracer uptake, but there was no statistically significant difference between them (46.65 ± 7.54 vs 25.15 ± 5.16, P = 0.252). Trop2 tumor proportion score and SUVmax were strongly correlated (Spearman correlation coefficient ρ = 0.88; R 2 = 0.64). Consequently, the following conclusions can be drawn: Trop2 immunoPET/CT offers superior diagnostic accuracy for PTC and metastatic lymph nodes, enhances surgical planning, and may revolutionize the clinical management of PTCs.