B2R-Targeting Radiotracer for PET/MR Imaging of Hepatocellular Carcinoma and Guiding Anti-B2R Therapy

The bradykinin B2 receptor (B2R) is overexpressed in a wide variety of tumors and is a well-defined target for tumor imaging and therapy. The hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) scanner is considered a noninvasive and advanced instrument for precise tumor imaging. In this work, we developed a novel B2R-targeting radiotracer, ⁶⁸Ga-DOTA-icatibant, for quantifying B2R expression. ⁶⁸Ga-DOTA-icatibant showed high stability, fast clearance and specific binding to B2R. PET/MR imaging revealed excellent tumor accumulation, and the uptake in tumors could be blocked by DOTA-icatibant. Icatibant-mediated anti-B2R therapy downregulated B2R expression in tumor cells and inhibited the growth of HepG2 tumors, and the decrease in tumor uptake was monitored by timely PET/MR imaging. Hematoxylin and eosin (H&E) and immunohistochemical staining results further demonstrated that the efficacy of anti-B2R could be accurately monitored with the developed PET/MR imaging radiotracer. ⁶⁸Ga-DOTA-icatibant can be utilized to noninvasively determine B2R expression and dynamically and sensitively monitor the efficacy of anti-B2R therapy.