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• W1567197268 abstract "ABSTRACT The serotonin subtype‐4 (5‐HT 4 ) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer's disease, anxiety, and other neuropsychiatric disorders—has few radioligands readily available for imaging in vivo. We have previously reported two novel 5‐HT 4 receptor radioligands, namely [ methoxy ‐ 11 C](1‐butylpiperidin‐4‐yl)methyl 4‐amino‐3‐methoxybenzoate; [ 11 C]RX‐1), and the [ 18 F]3‐fluoromethoxy analog ([ 18 F]RX‐2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5‐HT 4 receptor antagonist, on the same day for [ 11 C]RX‐1 and on different days for [ 18 F]RX‐2. Specific‐to‐nondisplaceable ratio ( BP ND ) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume ( V T ) was also measured in some monkeys by radiometabolite‐corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BP ND values were in the rank order of known 5‐HT 4 receptor distribution with a trend for higher BP ND values from [ 18 F]RX‐2. One‐tissue compartmental model provided good fits with well identified V T values for both radioligands. In the highest 5‐HT 4 receptor density region, striatum, 50–60% of total binding was specific. The V T in receptor‐poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [ 11 C]RX‐1 and [ 18 F]RX‐2 showed positive attributes for PET imaging of brain 5‐HT 4 receptors, validating the radioligand design strategy. Synapse 68:613–623, 2014 . © 2014 Wiley Periodicals, Inc." @default.
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• W1567197268 date "2014-08-11" @default.
• W1567197268 modified "2023-10-16" @default.
• W1567197268 title "Evaluation in monkey of two candidate PET radioligands, [¹¹C]RX-1 and [¹⁸F]RX-2, for imaging brain 5-HT₄receptors" @default.
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• W1567197268 doi "https://doi.org/10.1002/syn.21773" @default.
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