Radio-ligand receptor binding assay in vitro and animal biodistribution in vivo of ⁹⁹Tc^m-N-ethyl-N₂S₂-memantine as a potential NMDA receptor imaging agent

Radio-ligand receptor binding assay in vitro and animal biodistribution in vivo of 99 Tc m -N-ethyl-N 2 S 2 -memantine as a potential NMDA receptor imaging agent 1 first-author 2 2 corresp Corresponding author. E-mail address: jswxcgx@126.com Corresponding author. E-mail address: jswxcgx@126.com jswxcgx@126.com 2 2 2 2 Jiangnan University, School of Medicine and Pharmaceutics, Wuxi 214122, China Jiangnan University, School of Medicine and Pharmaceutics, Wuxi 214122, China Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China The pharmacologic characteristics of 99 Tc m -N-ethyl-N 2 S 2 -memantine, an NMDA receptor imaging agent, was investigated. It was prepared by a one-step reaction from N-ethyl-N 2 S 2 -memantine. The affinity and specificity were determined by radio-ligand receptor binding assay (RRA). Biodistribution in vivo in mice was performed. The results showed that 99 Tc m -N-ethyl-N 2 S 2 -memantine bound to a single site on NMDA receptor with a K d of 584.32 nmol/L and a B max of 267.05 nmol/mg. A competitive analysis showed that such specific binding could be inhibited by specific inhibitors of NMDA receptor, such as ketamine and (+)-MK-801. The biodistribution exhibited rapid uptake and favorable retention in mice brains. The major radioactivity was metabolized by the hepatic system. A two-compartment model of C = 4.49 e –0.083 t + 1.42 e –0.0016 t was established, and the half life was 8.35 min in blood. In conclusion, the new radio-ligand 99 Tc m -N-ethyl-N 2 S 2 -Memantine has a moderate affinity and specific binding to NMDA receptor, and can easily cross the blood-brain barrier (BBB). Therefore, it may be a potential NMDA receptor imaging agent. 99 Tc m -N-ethyl-N 2 S 2 -memantine NMDA receptor Radio-ligand receptor binding assay Biodistribution imaging References Yang Y , Wang X B , Frerking M , et al . Neurosci , 2008 , 28 ( 22 ): 5740 - 5751 . Neurosci Lin Y B , Zhao T J , Zhan Y. J . Biol ., 2007 , 24 ( 1 ): 1 - 4 . Biol Bendel O , Meijer B , Hurd Y , et al . Neurosci Lett , 2005 , 377 ( 1 ): 31 - 36 . Neurosci Lett Heather C , Paul L. C . Current Anaesthesia & Critical Care 2008 , 19 : 183 - 201 . Current Anaesthesia & Critical Care Garcia E , Schibli R , Schubiger P A . Nucl Sci Tech . 2007 , 18 : 88 - 100 . Nucl Sci Tech Ametamey S M , Samnick S , Leenders K L . Recept Signal Transduct Res , 1999 , 19 : 129 - 141 . Recept Signal Transduct Res Reynolds I J , Sharma T A . Methods Mol Biol , 1999 , 128 : 93 - 102 . Methods Mol Biol PENG S Y , YANG X Y , WANG W J . Chin Pharmacol Bull , 2004 , 20 ( 5 ): 585 - 587 . Chin Pharmacol Bull BAN T T , WU Q E , ZHOU Z J . Toxicol , 2007 , 21 ( 3 ): 231 - 232 . Toxicol Cao G X , Li W Y , Fang P . Chin J Nucl Med , 1987 , 7 ( 4 ): 217 - 219 . Chin J Nucl Med Mutel V , Buchy D , Klingelschmidt A , et al . Neurochem , 1998 , 70 ( 5 ): 2147 - 2155 . Neurochem Waterhouse R N , Abida S , Laruelle M . Nucl Medi Biol , 2002 , 29 : 791 - 794 . Nucl Medi Biol Matsumoto R , Haradahira T , Ito H , et al . Synapse , 2007 , 61 ( 10 ): 795 - 800 . Synapse Haradahira T , Zhang M R , Maeda J , et al . Nucl Med Biol , 2000 , 27 ( 4 ): 357 - 360 . Nucl Med Biol Xie Q , Hao J L , Qiu Z B . Chin Jour Pharmac , 2004 , 35 ( 5 ): 304 - 309 . Chin Jour Pharmac Seeman P , Ko F , Tallerico T . Mol Psychiatry , 2005 , 10 ( 9 ): 877 - 833 . Mol Psychiatry Waterhouse R N . Nucl Med Biol , 2003 , 30 ( 8 ): 869 - 878 . Nucl Med Biol Owens J , Wyper DJ , Patterson J , et al . Nucl Med Commun 1997 , 18 : 149 - 158 . Nucl Med Commun Ametamey S M , Bruehlmeier M , Kneifel S . Nucl Med Biol , 2002 , 29 : 227 - 231 . Nucl Med Biol 10.13538/j.1001-8042/nst.21.171-176 Supported by National Natural Science Foundation (No30770602) , Jiangsu Natural Science Foundation (No BK2008111) 2010-02-05 2010-06-20 2021-01-19 2010 Nuclear Science and Techniques 03 21