-(−)-[C]Epinephrine

-(–)-[C]Epinephrine ([C]EPI) is a radioligand developed for positron emission tomography (PET) imaging of the sympathetic nervous system (SNS) (1, 2, 11). It is a catecholamine analog labeled with C, a positron emitter with a physical half-life () of 20.4 min. Many diseases affect the SNS, and imaging of pathologic changes of adrenergic transmission has been an important area of PET research (3, 4). Most postganglionic sympathetic neurons in the autonomic nervous system release the neurotransmitter norepinephrine (NE), which stimulates adrenergic receptors in various effector organs (5). There are different types and subtypes of adrenergic receptors, and they are characterized as α to α, α to α, and β to β (6). All of the NE receptors belong to the G-protein-linked receptor superfamily and mediate slow neuromodulatory postsynaptic responses. The NE transporter (NET) is a transmembrane protein located in the adrenergic nerve terminals that is responsible for active reuptake (uptake-1) of NE released from neurons (7). NE is stored in the neuronal vesicles and is released on stimulation. Significant expression of NET is found in major organs of the SNS, such as the heart and brain. There is substantial evidence that aberrations in cardiac SNS function contribute to the morbidity and mortality associated with cardiac diseases (8). Molecular probes with structures closely related to NE can be used to assess the integrity of presynaptic sympathetic nerve terminals in various diseases. NE synthesis is similar to dopamine synthesis, and dopamine is converted to NE by the enzyme dopamine-β-hydroxylase (6). [I]--Iodobenzylguanidine ([I]MIBG), a single-photon emission tomography (SPECT) agent, has been developed and used for neuronal imaging (9). Efforts have been made to develop a positron-emitting tracer because of the inadequate quantitative information and lower spatial resolution obtained by SPECT imaging with [I]MIBG. EPI is a -methyl derivative of (–)-norepinephrine and is produced together with NE by the adrenal medulla and other chromaffin tissues (6, 9, 10). EPI is handled in a manner similar to that for NE, with binding to NET and transport by vesicular monoamine transporter into neuronal vesicles for storage. EPI is subject to metabolism by both monoamine oxidase and catechol--methyltransferase. Langer and Halldin (9) have reviewed and compared various PET and SPECT tracers for mapping the cardiac nervous system.