In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA   and 2-nitroimidazole-azide for tumor hypoxia targeting

doi:10.1016/j.bmcl.2015.09.004

CORC > 北京大学 > 化学与分子工程学院

	In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting
	Sun, Wenjing ; Chu, Taiwei
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2015
关键词	Tumor hypoxia 2-Nitroimidazole Tc-99m-labeling Pretargeting SPAAC AZIDE-ALKYNE CYCLOADDITION COPPER-FREE CLICK DEVELOPING ZEBRAFISH LIVING SYSTEMS LIVE MICE CHEMISTRY THERAPY TC-99M CANCER RADIOIMMUNOTHERAPY
DOI	10.1016/j.bmcl.2015.09.004
英文摘要	The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain-promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components: an azide group linked to 2-nitroimidazole (2NIM-Az) serves for tumor hypoxia- targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole-MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98 M-1 s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; Tc-99m-AM and Tc-99m-triazole-2NIM were used as blank control and conventional control. Compared to the control groups, the pretargeting experiment exhibits the best radio-uptake and retention in tumor, with higher tumor-to-muscle and tumor-to-blood ratios (up to 8.55 and 1.44 at 8 h post-Tc-99m-complex-injection, respectively). To some extent, the pretargeting strategy protects the bioactivity of nitroimidazole and therefore provides an innovative approach for the development of tumor hypoxia-SPECT imaging agents. (C) 2015 Elsevier Ltd. All rights reserved.; National Natural Science Foundation of China [21371017, 81371592]; SCI(E); PubMed; ARTICLE; twchu@pku.edu.cn; 20; 4453-4456; 25
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/415739]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Sun, Wenjing,Chu, Taiwei. In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2015.
APA	Sun, Wenjing,&Chu, Taiwei.(2015).In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS.
MLA	Sun, Wenjing,et al."In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2015).