Novel 99mTc labeled σ receptor ligand as a potential tumor imaging agent
Novel 99mTc labeled σ receptor ligand as a potential tumor imaging agent
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DOI：
10.1007/s11426-006-0169-z
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发表时间：
2006-04-01
期刊：
影响因子：
--
通讯作者：
Liu Boli
中科院分区：
文献类型：
--
作者：
Fan Caiyun;Jia Hongmei;Liu Boli
设计并制备了一种新型的Tc-99m标记配合物[N-[2-(（2-氧-2- 2-（4-（3-苯丙基）哌嗪-1-基）乙基]（2-巯基）氨基）乙酰基]-2-氨基乙炔乙酯]氧化锝（PPPE-MAMA' (TcO)-Tc-99m） （[Tc-99m]-2）。制备了相应的铼配合物PPPE-MAMA'-ReO （Re-2）并对其进行了表征。体外竞争结合实验显示，Re-2对sigma(1)和sigma(2)受体的K-i值分别为8.67 +/- 0.07和5.71 +/- 1.88 mu mol。在静脉注射后0.5 h、4 h、20 h获得的平面图像显示，在20 h时，[Tc-99m]-2在MCF-7人乳腺荷瘤小鼠体内积累。此外，在联合注射[Tc-99m]-2和氟哌啶醇（1 mg/kg）后20 h， [Tc-99m]-2的积累被抑制。生物分布研究显示，[Tc-99m]-2在静脉注射24小时后的体内肿瘤吸收量为0.14% +/- 0.01% ID/g，肿瘤/肌肉比为6.02 +/- 0.87。上述结果表明，源自先前发表的先导化合物的[Tc-99m]-2保留了一定的肿瘤摄取和对sigma受体的亲和力。[Tc-99m]-2可作为进一步结构修饰的基础，以开发对受体具有高亲和力的肿瘤显像剂。
A novel Tc-99m labeled complex, [N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(V) oxide (PPPE-MAMA' (TcO)-Tc-99m) ([Tc-99m]-2) has been designed and prepared based on the integrated approach. The corresponding rhenium complex (PPPE-MAMA'-ReO)(Re-2) has been prepared and characterized. In vitro competition binding assays show moderate affinity of Re-2 towards sigma(1) and sigma(2) receptors with K-i values of 8.67 +/- 0.07 and 5.71 +/- 1.88 mu mol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h after i.v. injection indicate the accumulation of [Tc-99m]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [Tc-99m]-2 has been inhibited at 20 h after co-injection of [Tc-99m]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [Tc-99m]-2 display an in vivo tumor uptake of 0.14% +/- 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of 6.02 +/- 0.87. The above results suggest that [Tc-99m]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for sigma receptors. [Tc-99m]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for a receptors.