A novel 11C-labeled thymidine analog, [11C]AZT, for tumor imaging by positron emission tomography

• DOI: 10.1186/s13550-015-0124-0
• Publication Date: 2015-09-03T01:55:43Z
• Authors: Tsuyoshi Tahara; Zhouen Zhang; Masahiro Ohno; Yukako Hirao; Nami Hosaka; Hisashi Doi; Masaaki Suzuki; Hirotaka Onoe
• Keywords: Cardiac Imaging; PET Imaging

Nucleoside analogs labeled with positrons, such as (11)C and (18)F, are considered valuable in visualizing the proliferative activity of tumor cells vivo using positron emission tomography (PET). We recently developed (11)C-labeled thymidine [(11)C]zidovudine ([(11)C]AZT) [(11)C]stavudine ([(11)C]d4T) via Pd(0)-Cu(I) co-mediated rapid C-C coupling reaction. In this study, to examine whether [(11)C]AZT [(11)C]d4T might be useful for visualization tumors vivo, we performed PET imaging, tissue distribution studies, metabolite analysis tumor-bearing mice.Mice bearing (rat glioma C6 human cervical adenocarcinoma HeLa cells) were injected 50 MBq or [(11)C]d4T, was immediately thereafter. After radioactivity several tissues, including measured a γ-counter. addition, radioactive metabolites plasma, bile, intestinal contents, analyzed thin layer chromatography (TLC). Cellular uptake presence absence non-labeled (0.1 mM).In mice clearly visualized [(11)C]AZT. Time-activity curves showed that accumulation plateaued at 10 min after injection persisted 60 min, while most other tissues rapidly excreted into urine. various body, highest 80 (five six times higher than blood). Compared tissue, lower spleen, intestine, bone marrow, resulting high tumor-to-bone marrow ratio. completely blocked by application thymidine, strongly indicating specific involvement nucleoside transporters. contrast, time-activity curve transient excretion almost no obvious accumulation.Tumors can detected [(11)C]AZT; therefore, could novel tracer imaging vivo.