Preparation and Biodistribution of Technetium-99m-Labeled Bis- Misonidazole (MISO) as an Imaging Agent for Tumour Hypoxia

Title:Preparation and Biodistribution of Technetium-99m-Labeled Bis- Misonidazole (MISO) as an Imaging Agent for Tumour Hypoxia

Volume: 11 Issue: 7

Author(s): Feng Wang, Di Fan, Jun Qian, Zhe Zhang, Jianhua Zhu and Jian Chen

Affiliation:

Keywords: Tumour hypoxia, imaging agent, misonidazole (MISO), technetium-99m-labeled.

Abstract: Diagnosis of tumour hypoxia is an important aspect in determining the course of tumour therapy. In this study, we developed a novel imaging agent, ^99mTcethylenedicysteine- bis-misonidazole (^99mTc-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 ^99mTc in the second step. ^99mTc-pertechnetate (^99mTcO4 -) 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 ^99mTc-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 ^99mTc-EC-MISO at 2 h. By introducing a second 2-nitroimidazole redox centre, an apparent hypoxic accumulation of this novel ^99mTc-labeled imaging agent in the tumour was observed.

Cite this article as:

Wang Feng, Fan Di, Qian Jun, Zhang Zhe, Zhu Jianhua and Chen Jian, Preparation and Biodistribution of Technetium-99m-Labeled Bis- Misonidazole (MISO) as an Imaging Agent for Tumour Hypoxia, Medicinal Chemistry 2015; 11 (7) . https://dx.doi.org/10.2174/1573406411666150504124103