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• W2140051058 abstract "The norepinephrine transporter (NET) is located presynaptically on noradrenergic nerve terminals and plays a critical role in the regulation of the synaptic norepinephrine (NE) concentration via the reuptake of NE. Changes in NET have been recently reported in several cardiac failures. Therefore, a NET-specific radioligand is useful for in vivo assessment of changes in NET density in various cardiac disorders. Recently, we developed a radioiodinated reboxetine analogue, (2S,αS)-2-(α-(2-iodophenoxy)benzyl)morpholine ((S,S)-IPBM), for NET imaging. In the current study, we assessed the applicability of radioiodinated (S,S)-IPBM to NET imaging in the heart. The NET affinity and selectivity were measured from the ability to displace specific [3H]nisoxetine and (S,S)-[125I]IPBM binding to rat heart membrane, respectively. To evaluate the distribution of (S,S)-[125I]IPBM in vivo, biodistribution experiment was performed in rats. With the use of several monoamine transporter binding agents, pharmacological blocking experiments were performed in rats. In vitro binding assays showed that the affinity of (S,S)-IPBM to NET was similar to those of the well-known NET-specific binding agents, nisoxetine and desipramine. Furthermore, (S,S)-[125I]IPBM binding was inhibited by nisoxetine and desipramine, but not by dopamine or serotonin transporter binding agents. These data indicated that (S,S)-IPBM had high affinity and selectivity for NET in vitro. Biodistribution studies in rats showed rapid and high uptake of (S,S)-[125I]IPBM by the heart and rapid clearance from the blood. The heart-to-blood ratio was 31.9 at 180 min after the injection. The administration of nisoxetine and desipramine decreased (S,S)-[125I]IPBM accumulation in the heart, but injection of fluoxetine and GBR12909 had little influence. Radioiodinated (S,S)-IPBM is a potential radioligand for NET imaging in the heart." @default.
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• W2140051058 date "2008-02-01" @default.
• W2140051058 modified "2023-10-11" @default.
• W2140051058 title "Evaluation of radioiodinated (2S,αS)-2-(α-(2-iodophenoxy)benzyl)morpholine as a radioligand for imaging of norepinephrine transporter in the heart" @default.
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• W2140051058 doi "https://doi.org/10.1016/j.nucmedbio.2007.11.006" @default.
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