Wang Feng, Fan Di, Qian Jun, Zhang Zhe, Zhu Jianhua, Chen Jian
School of Pharmacy, Fudan University, 826 Zhang Heng Rd., Shanghai 201203, PR China.
Med Chem. 2015;11(7):649-55. doi: 10.2174/1573406411666150504124103.
Diagnosis of tumour hypoxia is an important aspect in determining the course of tumour therapy. In this study, we developed a novel imaging agent, (99m)Tc-ethylenedicysteine-bis-misonidazole ((99m)Tc-EC-MISO), for diagnosing tumour hypoxia. We used 2-nitroimidazole as a reactant to synthesize the amino derivative of misonidazole (MISO) in the first step and then conjugated the di-amino derivative of MISO to the chelating agent ethylenedicysteine (EC) for labelling (99m)Tc in the second step. (99m)Tc-pertechnetate ((99m)TcO4-) was reduced by tin chloride (SnCl2) for radiolabeling. The radiochemical purity was up to 94%. Tissue biodistribution and SPECT/CT imaging studies were conducted on subcutaneous gliomal tumour-bearing mice. The tumour-to-muscle ratio in the (99m)Tc-EC-MISO group increased with time, up to 4.6 at 4 h after injection. SPECT/CT imaging confirmed that the tumours could be visualized clearly with (99m)Tc-EC-MISO at 2 h. By introducing a second 2-nitroimidazole redox centre, an apparent hypoxic accumulation of this novel (99m)Tc-labeled imaging agent in the tumour was observed.
肿瘤缺氧的诊断是确定肿瘤治疗方案的一个重要方面。在本研究中，我们开发了一种新型成像剂，即（99m）Tc-乙二半胱氨酸-双米索硝唑（（99m）Tc-EC-MISO），用于诊断肿瘤缺氧。第一步，我们使用2-硝基咪唑作为反应物合成米索硝唑（MISO）的氨基衍生物，然后在第二步中将MISO的二氨基衍生物与螯合剂乙二半胱氨酸（EC）偶联，用于标记（99m）Tc。用氯化亚锡（SnCl2）还原高锝酸盐（99m）TcO4-进行放射性标记。放射化学纯度高达94%。对皮下荷胶质瘤小鼠进行了组织生物分布和SPECT/CT成像研究。（99m）Tc-EC-MISO组的肿瘤与肌肉比值随时间增加，注射后4小时高达4.6。SPECT/CT成像证实，在2小时时，（99m）Tc-EC-MISO可清晰显示肿瘤。通过引入第二个2-硝基咪唑氧化还原中心，观察到这种新型（99m）Tc标记的成像剂在肿瘤中明显的缺氧蓄积。
