[F]1-(2-Fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine

[F]1-(2-Fluoroethyl)-4-[4-cyanophenoxy)methyl]piperidine ([F]SFE) is a radioligand developed for positron emission tomography (PET) imaging of the sigma (σ) receptors (1-3). F]SFE is a potent σ receptor agonist labeled with F, a positron emitter with a physical half-life () of 109.8 min. σ receptors are functional, membrane-bound, G-protein-coupled receptors distributed in the central nervous system (CNS) and peripheral organs (4). The CNS σ receptors are unique binding sites related to higher brain functions (5). They are distinct from opiate and phencyclidine binding sites. There are at least two subtypes of sigma receptors, σ and σ receptors. The precise mechanism of the functional response of these receptors is not entirely known. These receptors appear to be involved in numerous pharmacological and physiological functions, and they also modulate a number of central neurotransmitter systems, including noradrenergic, glutamatergic, and dopaminergic systems. Phencyclidine and derivatives, cocaine and derivatives, some neuroleptics, atypical antipsychotic agents, and other chemically unrelated compounds can bind to the σ receptor sites. Studies have shown that these receptors may play a role in the pathogenesis of psychiatric disorders (6, 7). These receptors are also expressed on a number of human and murine tumors (8). The σ receptor subtypes have a molecular weight of ≈25 kDa, and through the process of cloning they have shown a 30% sequence homology with the yeast C89-C7 sterol isomerase (4, 9, 10). The σ receptor subtypes have a molecular weight of ≈21.5 kDa, and have not been cloned. The σ receptors are thought to be involved in certain neuropsychiatric disorders, and the σ receptors are also implicated in malignant neoplastic diseases. Because of these effects, σ receptor ligands may be useful for detection and treatment in neurology and oncology. A number of ligands for these receptors have been labeled with C and F for PET imaging to map their brain distribution and expression on tumors (11). Waterhouse et al. (12, 13) synthesized a number of selective σ receptor ligands for both PET and single-photon emission computed tomography. [F]1-(3-Fluoropropyl)-4-(4-cyanophenoxy-methyl)piperidine ([F]FPS) was found to be a high-affinity σ receptor ligand with a dissociation constant () of 0.5 nM, but it was not cleared fast enough from the CNS to reach transient equilibrium by 4 h after administration in healthy volunteers (3). In an effort to improve the CNS clearance for PET studies, Zhao et al. (3) synthesized and evaluated [F]SFE ( = 5 nM), a analog of [F]FPS analog that exhibits a lower affinity for σ receptor ligands.