Structure–Activity Relationships of Azaquinazolinone Derivatives as ¹⁸ F-Labeled PET Probes Targeting Ghrelin Receptors

The ghrelin receptor (GHSR) is expressed in various organs including the brain, pancreas, stomach, and intestine, and is involved in many physiological functions. In vivo imaging of GHSR with positron emission tomography (PET) is expected to contribute to elucidation of the functions and pathophysiology of ghrelin-related diseases. In the present study, to develop novel PET probes targeting GHSR, we newly designed and synthesized 14 azaquinazolinone derivatives and evaluated their utility. Among them, AQ-12 showed the highest binding affinity for GHSR. In a biodistribution study using normal mice, [¹⁸F]AQ-12 displayed high uptake in the pancreas, which is one of the GHSR-expressing organs, and its radioactivity was significantly decreased by coinjection with unlabeled AQ-12. In addition, [¹⁸F]AQ-12 facilitated visualization of the pancreas in a normal mouse with PET/CT. These results suggest that [¹⁸F]AQ-12 has potential as a PET probe for in vivo imaging of GHSR.