PET Imaging of Sigma1 Receptors

Sigma receptors are classified into sigma1 and sigma2 subtypes. Sigma1 receptors are widely distributed in the central nervous system (CNS) and in peripheral tissues. Sigma1 receptors play a role in a variety of human CNS diseases, including mood disorders, stroke, neurodegenerative disease, and drug addiction. Therefore, there is a great deal of interest in imaging of sigma1 receptors in the living human brain. In contrast, sigma2 receptors have also been the focus of tumor imaging studies. A number of radioligands have been developed for imaging of sigma1 receptors in the human brain, and a few, including [11C]SA4503 and (-)-S-[18F]fluspidine, have been used in clinical studies. Sigma1 receptors are distributed throughout the grey matter of the human brain. A widespread decrease in [11C]SA4503 binding in patients with Alzheimer’s disease and a significant decrease in binding on the more affected side of the anterior putamen in patients with Parkinson’s disease have been reported. Receptor occupancy studies with [11C]SA4503-PET have shown that some antidepressants and antipsychotics have an affinity for sigma1 receptors in the human brain in addition to their main targets. Recently, it has been reported that the binding of (-)-S-[18F]fluspidine is increased in patients with untreated major depressive disorder (MDD).