In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004.
[updated ].


1-(4-[18F]Fluoroethoxy-3-methoxyphenethyl)-4-(3-phenylpropyl)piperazine ([18F]FE-SA4503) is a radioligand developed for positron emission tomography (PET) imaging of the sigma (σ) receptors. It is a potent sigma 1 (σ1) receptor agonist labeled with 18F, a positron emitter with a physical half-life (t½) of 109.8 min (1).

Sigma receptors are functional, membrane-bound proteins distributed in the central nervous system (CNS) and peripheral organs (2). The CNS sigma receptors are unique binding sites related to higher brain functions (3). They are distinct from opiate and phencyclidine (PCP) binding sites. There are at least two subtypes of sigma receptors, σ1 and σ2 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. PCP and derivatives, cocaine and derivatives, some neuroleptics, atyptical antipsychotic agents, and other chemically unrelated compounds can bind to the sigma receptor sites. Studies have shown that these receptors may play a role in pathogenesis of psychiatric disorders (4, 5)

The σ1 receptor subtypes appear to play in a role in motor functions and potassium channels (2). The σ2 receptor subtypes are implicated in CNS disorders and malignant neoplastic diseases. Because of these effects, sigma receptor ligands may be useful for the detection and treatment in neurology and oncology. Matsuno et al. (6) developed a potent σ1 agonist, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydrochloride (SA4503), which is in Phase II clinical trials as a therapeutic for functional recovery after stroke. SA4503 is highly selective for σ1 receptors than for σ2 receptors (6). Small modifications in the SA4503 structure appear to have profound effects on the σ12 receptor affinity and selectivity (1). SA5403 has been labeled with 11C for PET studies of sigma receptors in monkeys and humans (7-9). However, the equilibrium state of the receptor-ligand binding in monkeys was not possible to measure with [11C]SA4503 because of the short t½ of 11C. In an effort to overcome this problem, Elsinga et al. (1) synthesized [18F]FE-SA4503 with a longer physical t½ so that the equilibrium state of receptor-ligand binding can be studied.

Publication types

  • Review