| By virtue of its ideal nuclear physical characteristics for routine nuclear medicine diagnosis and its ready availability,technetium-99m is of outstanding interest in the development of novel radiopharmaceuticals. The potential for the development of 99mTc-based radioligands for study of the receptor function in central nervous system (CNS) is also well recognized despite the difficulties to be overcome.Based on the results of the data reported in literatures that exhibit high affinity for serotonin 5-HTIA,a free thiol ligand and two substitute arylpiperazines containing [99mTo] mixed-ligand complexes were designed and synthesized as a potential 5-HT1A receptor imaging agent.l-(2-methoxyphenyl)-(4-mercaptoethyl)-piperazine (MPMEP) as a monodentate,N,N-bis(2-mercaptoethyl)-N',N' diemyl-ethylenediamine (BMPDEEDA) and N,N-bis(2-mercaptoethyl)-benzylamine (BMPBA) as tridentate have been synthesized and characterized by IR,'H-NMR and elemental analysis. Both of new complexes,ReO(MPMEP)(BMPDEEDA) and ReO(MPMEP)(BMPBA),were synthesized by reacting MPMEP and SNS (BMPDEEDA and BMPBA) with ReOCl3(PPh3)2 in alkaline methanol solution,characterized by IR.'H-NMR and elemental analysis respectively. The single crystal structure of ReO(MPMEP)(BMPBA) was determined by X-ray diffraction method. It belongs to triclinic crystal system,adopts distorted trigonal bipyramidal geometry,with the basal plane defined by the SS atoms of tridentate ligand and the oxo-group. The N atom of the tridentate ligand and the S atom of the monodentate ligand occupy two apical positions.The desired 99mTc labeled compounds,99mTcCKMPMEPXBMPDEEDA) and 99mTcOtMPMEPXBMPBA) complexes were prepared via "3+1" mixed-ligand approach by using 99mTc-glucoheptonate as precursor. The labeling conditions were optimized to achieve high labeling yield. Both complexes were lipophilic and stable at room temperature. When challenged with cysteine (0.01,0.1 and 1.0 mM) or glutothione (0.01,0.1 and 1.0 mM) in phosphate buffer solution (lOOmM,pH 7.4),the 99mTo mixed-ligand complexes were,however,degraded rapidly. Biodistribution of two 99mTc complexes in mice showed higher brain uptake (1.63% ID/g and 1.77% ID/g at 2min) than the data reported in literature. The radioactivity retentions of 99mTcO(MPMEP)(BMPDEEDA) and 99mTcO(MPMEP)(BMPBA) in brain were 0.87% ID/g and0.46 % ID/g (at 60min),respectively. But the regional distribution of TcO(MPMEP)(BMPDEEDA) in Wistar rat's brain did not display selective localization,and the ratios of hippocampus to cerebellar were 0.847,0.880,0.921 and 1.244 at 30,60,120 and ISOmin post injection,respectively. Brain SPECT imaging studies in a monkey indicated that the uptakes of two complexes were low,but the uptake in the S-HT1A receptor-rich areas,for example,raphe nuclei,septum,cingulate and entorhinal cortex can be seen.The binding affinities of surrogate rhenium complex were tested in vitro competition assays against [3H]8-OH-DPAT.After introduced metallic chelate moiety,the arylpiperazine derivatives displayed moderate affinity for serotonin 5-HTiA receptor. ICso values of ReO(MPMEPXBMPDEEDA) and ReO(MPMEP)(BMPBA) were 98.9nM and 23.2 nM respectively.In addition,we also introduced the "99mTc(CO)3-core" to prepare 99mTo complex for serotonin 5-HT1A receptor imaging agent. The desired "99mTc(CO)3-core" complex was prepared by ligand-exchange reaction with [99mTc(CO)3(OH2)3]+. Biodistribution of 99mTc(CO)3CMPCEP) in mice showed high brain uptake (1.74% ID/g at 2min) and retention (0.96% ID/g at 60min).
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