A preliminary study on a new memantine derivative [^99mTc]- N-3,5-dimethyltricyclo[3,3,1]decanyl-2-((2-mercaptoethyl)(2-(2-mercaptoethylamino)-2-oxoethyl)amino)acetamide

Abstract

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Objectives: To develop a new technetium labeled ligand [^99mTc]- N-3,5-dimethyltricyclo[3,3,1]decanyl-2-((2-mercaptoethyl)(2-(2-mercaptoethylamino)-2-oxoethyl)amino)acetamide (^99mTc-NCAM) by using memantine coupled with N2S2 forming a stable complex as a potential SPECT imaging agent.

Methods: The labeling precursor N-3,5-dimethyltricyclo[3,3,1]decanyl-2-((2-mercaptoethyl) (2-(2-mercaptoethylamino)-2-oxoethyl)amino)acetamide was synthesized in a four-step reaction sequence. The chemical structures of the labeling precursor and its intermediates were verified by IR,NMR and MS. A series of studies were performed to optimize labeling efficiency of ^99mTc-NCAM.Radiochemical purity of ^99mTc-NCAM was measured by HPLC. Biodistribution was studied in normal mice (n=36).

Results: The octanol-water partition coefficient(logP)of ^99mTc-NCAM was 2.0 determined by HPLC. The complex showed electrically neutral evaluated by electrophoresis, and its molecular weight was 413 daltons. ^99mTc-NCAM was stable up to 6 h in aqueous solution and radiochemical purity was over 95% at selected condition. Biodistribution showed a fast clearance of radioactivity from blood. There was high brain uptake with increasing brain-blood ratios: 1.50, 4.95, 6.50, 6.87, 7.15 at 5, 30, 60, 120 ,240min, respectively.

Conclusions: These results indicate that ^99mTc –NCAM are favorable for transport through the BBB. It is probably a potential SPECT imaging agent and further study is needed.

Research Support: Project supported by National Natural Science Foundation of China (30770602), Key Project supported by Medical Science and Technology Development Foundation, Jiangsu Province Department of Health (K200512).