Synthesis and First Evaluation of [18F]Fluorocyano- and [18F]Fluoronitroquinoxalinedione as Putative AMPA Receptor Antagonists
Sebastian Olma, Johannes Ermert, Wiebke Sihver and Heinz H. Coenen
Pages 13-20 (8)
Derivatives of quinoxalinedione (QX) were chosen as chemical lead for the development of new radioligands
of the AMPA receptor, since there are several examples of QX-derivatives with high affinity. The radiosyntheses of the
new compounds 6-[18F]fluoro-7-nitro-QX ([18F]FNQX) and 7-[18F]fluoro-6-cyano-QX ([18F]FCQX) with radiochemical
yields of 8 ± 2 and 3 ± 2 %, respectively, as well as the evaluation of their binding properties to the AMPA-receptor were
performed. A comparison of the Ki-values of the new QX-derivatives FCQX and FNQX with mono-substituted cyanoand
nitro-QX shows negligibly small differences of affinity (within the range of 1.4 to 5 µM), but exhibits a tenfold lower
affinity than derivatives with two electron withdrawing groups like the 7-cyano-6-nitro-compound CNQX and the 6,7-
dinitro compound DNQX. Thus, with respect to the low affinity and a high non-specific binding with in vitro and ex vivo
autoradiographic studies, the new compounds do not lend themselves for in vivo imaging.
AMPA receptor, fluorine-18, glutamate receptor, positron emission tomography, quinoxalinedione, radiofluorination.
Institut fur Neurowissenschaften und Medizin, INM-5: Nuklearchemie, Forschungszentrum Julich GmbH, 52425 Jülich, Germany.