First-in-class Trop2-targeted PET imaging with ⁶⁸ Ga-MY6349 for diagnostic accuracy and altered management in recurrent/metastatic thyroid cancer compared to standard ¹⁸ F-FDG PET/CT.

6041 Background: Accurate, non-invasive detection of recurrent and metastatic thyroid cancer remains an unmet clinical need due to the limitations of conventional imaging and biopsy. Trop2 is a tumor-associated antigen that frequently overexpressed in thyroid cancer, it represents a promising molecular target for imaging. This study aimed to evaluate the diagnostic accuracy of Trop2-targeted PET/CT using the novel nanobody tracer, 68 Ga-MY6349, the results were compared with those of 18 F-FDG PET/CT. Methods: In this prospective, single-center, single-arm trial conducted at the First Affiliated Hospital of Xiamen University (Xiamen, China), adults with suspected or confirmed recurrent or metastatic thyroid cancer were enrolled between January and December 2024. Each participant underwent both 68 Ga-MY6349 and 18 F-FDG PET/CT scans within one week. Three independent, blinded readers assessed the PET/CT images. The primary endpoints were patient-based sensitivity and specificity, using histopathology or clinical follow-up as the reference standard. The full analysis set included patients with evaluable PET/CT imaging and a confirmed final diagnosis. The trial is registered with ClinicalTrials.gov, NCT06465017 and is closed to enrollment. Results: Of 161 screened participants, 143 were finally included in the primary analysis. Papillary thyroid cancer (PTC) was the most common pathological subtype (115/143, 80%). The median clinical follow-up duration was 19 months (IQR: 14-22 months). In the overall cohort, the sensitivity and specificity of 68 Ga-MY6349 PET/CT was 90% (95% CI 83-94) and 91% (95% CI 76-97), respectively. Among participants with PTC, its sensitivity and specificity were 94% (95% CI, 87–98) and 96% (95% CI, 79–100), respectively. Additionally, 68 Ga-MY6349 PET/CT demonstrated superior diagnostic accuracy in participants with thyroglobulin-elevated negative iodine scintigraphy (TENIS), with sensitivity of 92% (95% CI 82-97) and accuracy of 93% (95% CI 84-97), respectively. Further details are presenting in the Table. No grade 2 or higher adverse event was observed during study. Conclusions: 68 Ga-MY6349 PET/CT is a safe and highly accurate imaging modality for detecting recurrent and metastatic thyroid cancer, particularly in PTC and patients with TENIS. These findings suggest it could significantly influence clinical practice and may become a standard imaging option in this setting. Further multicenter studies are warranted to validate its diagnostic accuracy and assess its long-term impact on patient management and outcomes. Clinical trial information: NCT06465017 .