Novel 18F-Labeled PET Tracers Specific to Aromatase: Design, Synthesis, and Biological Evaluation

The abnormal expression of aromatase is associated with the occurrence and development of a variety of neurological diseases and tumors. A series of F-18-labeled and Ga-68-labeled potential aromatase-binding candidate compounds were designed and synthesized based on the structures of aromatase inhibitors. Competitive inhibition experiments in vitro and molecular docking showed that BIBD-069 and BIBD-071 have high affinity for aromatase. The radiolabeling conditions of [F-18]BIBD-069 and [F-18]BIBD-071 were simple, and the yields were high. Biodistribution and in vivo inhibition experiments confirmed that [F-18]BIBD069 and [F-18]BIBD-071 specifically bind to aromatase. [F-18]BIBD-069 and [F-18]BIBD-071 selectively imaged the amygdala and nucleus of the stria terminalis, which is similar to the imaging result of [C-11]vorozole. Radiometabolites of [F-18]BIBD-069 and [F-18]BIBD-071 did not bind to aromatase and interfered with brain imaging. MicroPET-CT imaging further confirmed that [F-18]BIBD-069 and [F-18]BIBD-071 can specifically bind to aromatase and were not defluorinated in vivo. Given that [F-18]BIBD-069 and [F-18]BIBD-071 exhibit excellent aromatase binding affinities, mild radiolabeling conditions, and good pharmacokinetics, they can be important tools for the diagnosis and treatment of aromatase-related diseases.

Automated summary

The abnormal expression of aromatase is associated with various neurological diseases and tumors. In this study, F-18 and Ga-68 labeled compounds were designed and synthesized to bind to aromatase. Two of these compounds, BIBD-069 and BIBD-071, showed high affinity for aromatase. They were successfully radiolabeled and specifically bound to aromatase in vitro and in vivo. These compounds can serve as important tools for the diagnosis and treatment of aromatase-related diseases.