Author(s)

F. Caille, T. J. Morley, A. A. Tavares, C. Papin, N. M. Twardy, D. Alagille, H. S. Lee, R. M. Baldwin, J. P. Seibyl, O. Barret, G. D. Tamagnan

ISBN

1464-3405 (Electronic) 0960-894X (Linking)

Publication year

2013

Periodical

Bioorg Med Chem Lett

Periodical Number

23

Volume

23

Pages

6243-7

Author Address

Molecular NeuroImaging LLC, New Haven, CT 06510, USA; Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.

Full version

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.