Preparation and Biodistribution of Technetium-99m-Labeled Bis- Misonidazole (MISO) as an Imaging Agent for Tumour Hypoxia.
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.
Feng
F
Wang
Di
D
Fan
Jun
J
Qian
Zhe
Z
Zhang
Jianhua
J
Zhu
School of Pharmacy, Fudan University, 826 Zhang Heng Rd., Shanghai 201203, PR China. jianchen@fudan.edu.cn.
Jian
J
Chen
D000818:Animals; D001345:Autoradiography; D015687:Cell Hypoxia; D005910:Glioma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008920:Misonidazole / Q000737:chemistry* / Q000493:pharmacokinetics*; D009821:Oils / Q000737:chemistry; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014867:Water / Q000737:chemistry
D009821:Oils; D014867:Water; D013667:Technetium; D008920:Misonidazole