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

RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE

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

LIU Yingtao，

ZHOU Xingqin，

CAO Guoxian，

ZHANG Jiankang，

QIN Xiaofeng，

XU Xijie，

ZOU Meifen

Nuclear Science and Techniques

Vol.21, No.3

pp.171-176

Published in print 20 Jun 2010

DOI：10.13538/j.1001-8042/nst.21.171-176

47500

The pharmacologic characteristics of ⁹⁹Tc^m-N-ethyl-N₂S₂-memantine, an NMDA receptor imaging agent, was investigated. It was prepared by a one-step reaction from N-ethyl-N₂S₂-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 ⁹⁹Tc^m-N-ethyl-N₂S₂-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 = 4.49e^–0.083t + 1.42e^–0.0016t was established, and the half life was 8.35 min in blood. In conclusion, the new radio-ligand ⁹⁹Tc^m-N-ethyl-N₂S₂-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.

99Tcm-N-ethyl-N2S2-memantineNMDA receptorRadio-ligand receptor binding assayBiodistributionimaging

References

[1]

Yang Y, Wang X B, Frerking M, et al. Neurosci, 2008, 28(22): 5740-5751.

[2]

Lin Y B, Zhao T J, Zhan Y. J. Biol., 2007, 24(1):1-4.

[3]

Bendel O, Meijer B, Hurd Y, et al. Neurosci Lett, 2005, 377(1): 31-36.

[4]

Heather C, Paul L. C. Current Anaesthesia & Critical Care 2008, 19: 183-201.

[5]

Garcia E, Schibli R, Schubiger P A. Nucl Sci Tech. 2007, 18: 88-100.

[6]

Ametamey S M, Samnick S, Leenders K L. Recept Signal Transduct Res, 1999, 19: 129-141.

[7]

Reynolds I J, Sharma T A. Methods Mol Biol, 1999, 128: 93-102.

[8]

PENG S Y, YANG X Y, WANG W J. Chin Pharmacol Bull, 2004, 20(5): 585-587.

[9]

BAN T T, WU Q E, ZHOU Z J. Toxicol, 2007, 21(3): 231-232.

[10]

Cao G X, Li W Y, Fang P. Chin J Nucl Med, 1987, 7(4): 217-219.

[11]

Mutel V, Buchy D, Klingelschmidt A, et al. Neurochem, 1998, 70(5):2147-2155.

[12]

Waterhouse R N, Abida S, Laruelle M. Nucl Medi Biol, 2002, 29:791-794.

[13]

Matsumoto R, Haradahira T, Ito H, et al. Synapse, 2007, 61(10): 795-800.

[14]

Haradahira T, Zhang M R, Maeda J, et al. Nucl Med Biol, 2000, 27(4): 357-360.

[15]

Xie Q, Hao J L, Qiu Z B. Chin Jour Pharmac, 2004, 35(5): 304-309.

[16]

Seeman P, Ko F, Tallerico T. Mol Psychiatry, 2005, 10(9): 877-833.

[17]

Waterhouse R N. Nucl Med Biol, 2003, 30(8): 869-878.

[18]

Owens J, Wyper DJ, Patterson J, et al. Nucl Med Commun 1997, 18:149-158.

[19]

Ametamey S M, Bruehlmeier M, Kneifel S. Nucl Med Biol, 2002, 29: 227-231.