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
Affiliation: Institut fur Neurowissenschaften und Medizin, INM-5: Nuklearchemie, Forschungszentrum Julich GmbH, 52425 Jülich, Germany.
Keywords: AMPA receptor, fluorine-18, glutamate receptor, positron emission tomography, quinoxalinedione, radiofluorination.
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.
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