Carbonic Anhydrase IX-Targeted Molecular Probe for Positron Emission Tomography Imaging of Clear Cell Renal Cell...

Carbonic anhydrase IX (CAIX) has been considered as a promising biomarker for diagnosing and treating clear cell renal cell carcinoma (ccRCC). Therefore, sensitive and accurate detection of the CAIX expression level is crucial for guiding therapeutic decisions and prognostic assessment of ccRCC. In this study, a small molecular imaging probe, ¹⁸F-DAZ, was designed and synthesized for specifically and sensitively visualizing CAIX expression in vivo. ¹⁸F-DAZ exhibited high radiochemical purity (>98%), high stability, and high affinity for CAIX-positive cancer cells OS-RC-2 with the K _d value of 69.09 ± 12.16 nM. The probe uptake in OS-RC-2 cells (2.52 ± 0.20%AD) was higher than that in the OS-RC-2 blocking group (0.94 ± 0.12%AD) and CAIX-negative cells HCT-116 (0.82 ± 0.19%AD) at the same time. PET imaging results showed that the highest accumulation of the probe in OS-RC-2 bearing mice (3.29 ± 0.16%ID/mL) was also markedly higher than that in the OS-RC-2 blocking group (1.34 ± 0.12%ID/mL) and HCT-116 (1.26 ± 0.03%ID/mL). Biodistribution and autoradiography analysis further verified that the probe ¹⁸F-DAZ can specifically target CAIX. These results highlight the potential of ¹⁸F-DAZ as a candidate PET imaging radiotracer for detecting CAIX-overexpressing tumors.