Nanobody-Based PET Imaging of CD47 Expression in Thyroid Carcinoma

Thyroid cancer is the most common malignant tumor in the endocrine system. A significant correlation has been established between elevated CD47 expression and the progression of thyroid carcinoma. This study aims to evaluate the diagnostic potential of immuno-positron emission tomography (immunoPET) utilizing CD47-targeting nanobodies in thyroid cancer tumor models. Immunohistochemistry (IHC) was employed to evaluate CD47 expression in patients with thyroid cancer, as well as in anaplastic thyroid carcinoma (ATC) xenograft tumor (OCUT-2C) and differentiated thyroid cancer (DTC) xenograft tumors (TPC-1 and BCPAP). Two nanobodies, C2 and its albumin-binding derivative (ABDC2), specifically targeting CD47 were labeled with 68 Ga. The tracers were evaluated using immunoPET imaging in models of thyroid cancer. IHC revealed that CD47 was highly expressed in 34.69% of the tumor tissues from patients with thyroid cancer. Additionally, high levels of CD47 expression were observed in OCUT-2C, TPC-1, and BCPAP tumor tissues. Micro-PET imaging using [ 68 Ga]Ga-NOTA-C2 and [ 68 Ga]Ga-NOTA-ABDC2 demonstrated clear visualization of OCUT-2C tumors. Notably, the tumor uptake of [ 68 Ga]Ga-NOTA-ABDC2 was significantly higher than that of [ 68 Ga]Ga-NOTA-C2 at each imaging time point. Additionally, [ 68 Ga]Ga-NOTA-ABDC2 exhibited specific uptake in the TPC-1 and BCPAP models. This study confirmed that [ 68 Ga]Ga-NOTA-ABDC2 as a innovative PET imaging radiotracer targeting CD47 presented specific and higher tumor uptake to accurately identify CD47 expression and diagnose thyroid cancer. The clinical application of these imaging strategies may aid in selecting patients for CD47-targeted therapies and evaluating their subsequent responses.