Synthesis and first evaluation of [¹⁸F]fluorocyano- and [¹⁸F]fluoronitro-quinoxalinedione as putative AMPA receptor antagonists.
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-[(18)F]fluoro-7-nitro-QX([(18)F]FNQX) and 7-[(18)F]fluoro-6-cyano-QX ([(18)F]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.
Sebastian
S
Olma
Johannes
J
Ermert
Wiebke
W
Sihver
Institut fur Neurowissenschaften und Medizin, INM-5: Nuklearchemie, Forschungszentrum Julich GmbH, 52425 Jülich, Germany. j.ermert@fz-juelich.de.
Heinz H
HH
Coenen
D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005462:Fluorine Radioisotopes; D007700:Kinetics; D051379:Mice; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011810:Quinoxalines / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013194:Staining and Labeling
D018691:Excitatory Amino Acid Antagonists; D005462:Fluorine Radioisotopes; D009574:Nitro Compounds; D011810:Quinoxalines; D018091:Receptors, AMPA