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

Abstract

The abnormal expression of aromatase is associated with the occurrence and development of a variety of neurological diseases and tumors. A series of ¹⁸F-labeled and ⁶⁸Ga-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 [¹⁸F]BIBD-069 and [¹⁸F]BIBD-071 were simple, and the yields were high. Biodistribution and in vivo inhibition experiments confirmed that [¹⁸F]BIBD-069 and [¹⁸F]BIBD-071 specifically bind to aromatase. [¹⁸F]BIBD-069 and [¹⁸F]BIBD-071 selectively imaged the amygdala and nucleus of the stria terminalis, which is similar to the imaging result of [¹¹C]vorozole. Radiometabolites of [¹⁸F]BIBD-069 and [¹⁸F]BIBD-071 did not bind to aromatase and interfered with brain imaging. MicroPET-CT imaging further confirmed that [¹⁸F]BIBD-069 and [¹⁸F]BIBD-071 can specifically bind to aromatase and were not defluorinated in vivo. Given that [¹⁸F]BIBD-069 and [¹⁸F]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.

Keywords: BIBD-069/071; YM511; aromatase; positron emission tomography; tracer.