Nuclear Science and Techniques

《核技术》(英文版) ISSN 1001-8042 CN 31-1559/TL     2019 Impact factor 1.556

Nuclear Science and Techniques ›› 2013, Vol. 24 ›› Issue (3): 030303 doi: 10.13538/j.1001-8042/nst.2013.03.009

• NUCLEAR CHEMISTRY,RADIOCHEMISTRY,RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE • Previous Articles     Next Articles

Preparation of 99mTc-PQQE and preliminary biological evaluation for the NMDA receptor

ZHOU Xingqin  KONG Yanyan  ZOU Meifen  ZHANG Jiankang  CAO Guoxian   

  1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China
  • Received:2013-04-08
  • Contact: ZHOU Xingqin E-mail:zhouxingqin@jsinm.org
  • Supported by:

    Supported by National Natural Science Foundation of China (No.30770602) and Natural Science Foundation of Jiangsu Province, China (Nos. BK2010157 and BK2011167)

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ZHOU Xingqin, KONG Yanyan, ZOU Meifen, ZHANG Jiankang, CAO Guoxian . Preparation of 99mTc-PQQE and preliminary biological evaluation for the NMDA receptor.Nuclear Science and Techniques, 2013, 24(3): 030303     doi: 10.13538/j.1001-8042/nst.2013.03.009

Abstract:

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). 99mTc-PQQE was prepared using stannous fluoride (SnF2) as reducing agent. Biological characteristics of 99mTc-PQQE include lipophilic and the charge properties were compared to 99mTc-PQQ. The biodistributions of 99mTc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99mTc-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 (t1/2β) results indicate that the residence time of 99mTc-PQQE (203.92) in the body is twice as long as 99mTc-PQQ (100.45). The uptake of 99mTc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99mTc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99mTc-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 99mTc-PQQE has some specific targeting to the NMDA receptor.

 

Key words: Key words , PQQE, 99mTc-PQQE, NMDA receptor, Bodistribution, in vitro autoradiography assay