In the central nervous system, 5-HT4 receptors are primarily localized in the limbic and nigro-striatal pathways implicate in learning and memory. Preclinical evidence have shown that 5-HT4 agonists increase acetylcholine release in these brain regions resulting in cognitive improvement in animal model of Alzheimer's disease (AD). Moreover, a decrease in 5-HT4 receptors in the hippocampus was observed, post mortem, in Alzheimer's disease patients. These findings emphasize the need for non-invasive scintigraphic methods for assessing new drug targeting 5-HT4 receptors and elucidating their pathophysiological changes in AD patients. We present the radiosynthesis, in vitro and in vivo evaluation of a novel [18F]fluorinated benzodioxane derivatives [18F]MNI-698, analogue of the selective antagonist SB204070. [18F]MNI-698 was obtained following a two steps radiolabelling procedure with a 4�1% radiochemical yield and a radiochemical purity above 98%. Brain distribution of [18F]MNI-698 by PET imaging in non human primates were in accordance with reported distribution of 5-HT4. [18F]MNI-698 shows the highest brain uptake in the striatum (7 SUV), follow by the hippocampus and substantia nigra (5.5 and 5 SUV respectively). Blockade study using SB204070 demonstrates the specificity of the signal, suggesting that [18F]MNI-698 is a promising candidate for human imaging of 5-HT4 receptors.

Synthesis and evaluation of a new positron emission tomography (PET) radioligands for 5-HT<sub>4</sub> imaging in nonhuman primate: [<sup>18</sup>F]MNI-698

245th National Meeting (2013)

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Synthesis and evaluation of a new positron emission tomography (PET) radioligands for 5-HT4 imaging in nonhuman primate: [18F]MNI-698

Synthesis and evaluation of a new positron emission tomography (PET) radioligands for 5-HT₄ imaging in nonhuman primate: [¹⁸F]MNI-698