Synthesis and biological evaluation of positron emission tomography radiotracers targeting serotonin 4 receptors in brain: [18F]MNI-698 and [18F]MNI-699.

Authors :: Caillé F
Morley TJ
Tavares AA
Papin C
Twardy NM
Alagille D
Lee HS
Baldwin RM
Seibyl JP
Barret O
Tamagnan GD
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Dec 01; Vol. 23 (23), pp. 6243-7. Date of Electronic Publication: 2013 Oct 09.
Publication Year :: 2013
Abstract: Two new benzodioxane derivatives were synthesized as candidates to image the serotonin 4 receptors by positron emission tomography (PET) and radiolabeled with fluorine-18 via a two-step procedure. Competition binding assays demonstrated that MNI-698 and MNI-699 had sub-nanomolar binding affinities against rat striatal 5-HT4 receptors (Ki of 0.20 and 0.07 nM, respectively). PET imaging in rhesus monkey showed that the regional brain distribution of [(18)F]MNI-698 and [(18)F]MNI-699 were consistent with the known densities of 5-HT4 in brain. [(18)F]MNI-698 and [(18)F]MNI-699 are among the first fluorine-18 radiotracers developed for imaging the 5-HT4 receptors in vivo and are currently under preclinical investigation in primates for future human use.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Subjects :: Animals
Binding, Competitive
Brain metabolism
Dioxanes chemistry
Macaca mulatta
Piperidines chemistry
Positron-Emission Tomography methods
Radiopharmaceuticals chemistry
Radiopharmaceuticals metabolism
Rats
Receptors, Serotonin, 5-HT4 metabolism
Brain diagnostic imaging
Dioxanes chemical synthesis
Fluorine Radioisotopes chemistry
Piperidines chemical synthesis
Radiopharmaceuticals chemical synthesis
Receptors, Serotonin, 5-HT4 analysis

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