[C]Norepinephrine

[C]Norepinephrine ([C]NE) is a radioligand developed for positron emission tomography (PET) imaging of the sympathetic nervous system (SNS). It is a catecholamine analog labeled with C, a positron emitter with a physical half-life () of 20.4 min (1). Many diseases affect the SNS, and imaging of pathologic changes of adrenergic transmission has been an important area of PET research (2, 3). Most postganglionic sympathetic neurons in the autonomic nervous system release the neurotransmitter norepinephrine (NE), which stimulates adrenergic receptors in various effector organs (4). There are different types of adrenergic receptors, and NE stimulates α, β, and certain β receptors. 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 (5). 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 (6). Molecular probes with structures closely related to NE can be used to assess the integrity of presynaptic sympathetic nerve terminals in various diseases. [I]-Iodobenzylguanidine ([I]MIBG), a single-photon emission tomography (SPECT) agent, has been developed and used for neuronal imaging (7). 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 (7). Studies with [C]NE and [H]NE have shown that when radiolabeled NE was injected intravenously into animals, NE rapidly disappeared from the circulation and accumulated in organs rich in SNS (7, 8). NE is taken up by NET and transported by vesicular monoamine transporter into storage vesicles. However, radiolabeled NE is subject to metabolism by both monoamine oxidase and catechol--methyl transferase. Langer and Haldin (7) reviewed and compared various PET and SPECT trances for mapping the cardiac nervous system.