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KMID : 1145520190050010018
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Journal of Radiopharmaceuticals and Molecular Probes
2019 Volume.5 No. 1 p.18 ~ p.25
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Evaluation of 99mTc-MAG3-2-nitroimidazole for hypoxic tumor imaging
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Lee Yun-Sang
Kim Young-Joo
Jeong Jae-Min
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Abstract
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2-Nitroimidazole derivatives have been reported to accumulate in hypoxic tissue. We prepared a novel 99mTcMAG3-2-nitroimidazole and evaluated the feasibility for hypoxia imaging agent. Bz-MAG3-2-nitroimidazole was synthesized by direct coupling of Bz-MAG3 and 2-nitroimidazole using dicyclohexylcarbodiimide. Bz-MAG3-2-nitroimidazole was labeled with 99mTc in the presence of tartaric acid and SnCl2-2H2O at 100°C for 30 min. And the reaction mixture was purified by C18 Sep-pak cartridge. The labeling efficiency and the radiochemical purity were checked by ITLC-SG/acetonitrile. The tumor was grown in balb/c mice for 8~13 days after the subcutaneous injection of tumor cells, CT-26 (murine colon adenocarcinoma cell). Biodistribution study and tumor autoradiography were performed in the xenografted mice after i.v injection of 74 kBq/0.1 mL and 19 MBq/0.1 mL of 99mTc-MAG3-2-nitroimidazole, respectively. In vivo images of 99mTc-MAG3-2-nitroimidazole in tumor bearing mice were obtained 1.5 hr post injection. The labeling efficiency was 45±20% and the radiochemical purity after purification was over 95%. Paper electrophoresis confirmed negative charge of 99mTc-MAG3-2-nitroimidazole. 99mTc-MAG3-2-nitroimidazole was very stable at room temperature and its protein binding was 53%. The 99mTc-MAG3-2-nitroimidazole exhibited high uptake in the liver, stomach and intestine. In biodistribution study using tumor bearing mice, the uptakes (% ID/g) of the tumor were 0.5±0.1, 0.4±0.0, 0.2±0.1 and 0.1±0.1 at 5, 15, 30 min and 4 hrs. Tumor/muscle ratio were 1.4±0.1, 2.2±0.83, 3.0±0.9, and 3.7 (n=2) for 5, 15, 30 min and 4 hrs. The uptake in hypoxic area was found higher than in non-hypoxic area of tumor tissue by autoradiography. In vivo images showed the relatively faint uptake to the hypoxic tumor region. 99mTc-MAG3-2-nitroimidazole was successfully synthesized and found feasible for imaging hypoxia.
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KEYWORD
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Technetium-99m, 2-Nitroimidazole, MAG3, Hypoxia, Tumor imaging
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