Preparation Of Tc-99m-Pqqe And Preliminary Biological Evaluation For The Nmda Receptor

The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). Tc-99m-PQQE was prepared using stannous fluoride (SnF2) as reducing agent. Biological characteristics of Tc-99m-PQQE include lipophilic and the charge properties were compared to Tc-99m-PQQ. The biodistributions of Tc-99m-PQQE in mice and brain regional distribution were performed. In vivo distribution of Tc-99m-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2 beta) results indicate that the residence time of Tc-99m-PQQE (203.92) in the body is twice as long as Tc-99m-PQQ (100.45). The uptake of Tc-99m-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of Tc-99m-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. Tc-99m-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that Tc-99m-PQQE has some specific targeting to the NMDA receptor.