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PET Imaging of F-18-(2S,4R)4-Fluoroglutamine Accumulation in Breast Cancer: From Xenografts to Patients
Liu, Fei1; Xu, Xiaoxia1; Zhu, Hua1; Zhang, Yan2; Yang, Jianhua1; Zhang, Lifang2; Li, Nan1; Zhu, Lin2; Kung, Hank F.3,4; Yang, Zhi1
通讯作者Kung, Hank F.(3,4) ; Yang, Zhi(1)
关键词glutamine PET breast cancer metabolic imaging Myc
刊名MOLECULAR PHARMACEUTICS
2018-08-01
DOI10.1021/acs.molpharmaceut.8b00430
15期:8页:3448-3455
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]GLUTAMINE-METABOLISM ; NEOADJUVANT CHEMOTHERAPY ; MYC ; CELLS ; INHIBITOR ; GROWTH ; DIFFERENTIATION ; EXPRESSION ; TUMORS ; MRI
英文摘要

Sustaining the growth of tumor cells requires extra energy and metabolic building blocks. In addition to consuming glucose, glutamine may play the role as an alternative source of nutrient for growth and survival. We aim to characterize a glutamine analog, F-18-(2S,4R)4-fluoroglutamine (F-18-(2S,4R)4-FGln), as an imaging agent for interrogating the role of glutamine from the in vitro study of tumor cells to clinical manifestation in breast cancer patients. Purity was measured by radio-high-performance liquid chromatography (radio-HPLC), and the stability after production was evaluated in phosphate buffer saline (PBS), saline, and mouse and human serum buffers. The presence of Myc expression in MCF-7 and U87 cells was conducted using qPCR In vitro cell uptake of F-18-(2S,4R)4-FGln in MCF-7 and U87 cells was directly compared with F-18-fluorodeoxyglucose (F-18-FDG). In vivo biodistribution and micro-PET imaging of F-18-(2S,4R)4-FGln in MCF-7 bearing BALB/c nude mice were performed. PET/CT imaging of F-18-(2S,4R)4-FGln was compared with F-18-FDG in the same group of breast cancer patients (n = 10). We successfully synthesized F-18-(25,4R)4-FGln with a high radiochemical purity (>98%), and the radiochemical purity was unchanged in PBS and saline buffers during a 2 h incubation. In vitro cell uptake studies of 18F(25,4R)4-FGln displayed a rapid and higher uptake in MCF-7 and U87 cells as compared with F-18-FDG. Biodistribution and micro-PET images showed excellent tumor accumulation of F-18-(2S,4R)4-FGln in the MCF-7-implanted mice tumor model. In a preliminary clinical study, F-18-(2S,4R)4-FGln/PET detected more lesions in breast cancer patients than F-18-FDG/PET (90% vs 80%). Additionally, in one patient with breast lobular carcinoma, there was a lesion mean standardized uptake value (SUI/mean) and maximum standardized uptake value (SUVmax) for F-18-(2S,4R)4-FGIn higher than those obtained by F-18-FDG, as determined by PET imaging. (25,4R)4-FGln may be a useful glutamine-targeting metabolic probe for noninvasive imaging of breast cancer.

语种英语
WOS记录号WOS:000441476800055
通讯作者邮箱kunghf@pennmedicine.upenn.edu ; pekyz@163.com
第一作者单位Peking Univ Canc Hosp & Inst, Dept Nucl Med, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China
通讯作者单位Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA ; Peking Univ Canc Hosp & Inst, Dept Nucl Med, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China ; Capital Med Univ, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China
ISSN1543-8384
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/142883
专题北京大学临床肿瘤学院_核医学科
作者单位1.Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA;
2.Peking Univ Canc Hosp & Inst, Dept Nucl Med, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China;
3.Beijing Normal Univ, Coll Chem, Key Lab Radiopharmaceut, Minist Educ, Beijing 100875, Peoples R China;
4.Capital Med Univ, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China
推荐引用方式
GB/T 7714
Liu, Fei,Xu, Xiaoxia,Zhu, Hua,et al. PET Imaging of F-18-(2S,4R)4-Fluoroglutamine Accumulation in Breast Cancer: From Xenografts to Patients[J]. MOLECULAR PHARMACEUTICS,2018,15(8):3448-3455.
APA Liu, Fei.,Xu, Xiaoxia.,Zhu, Hua.,Zhang, Yan.,Yang, Jianhua.,...&Yang, Zhi.(2018).PET Imaging of F-18-(2S,4R)4-Fluoroglutamine Accumulation in Breast Cancer: From Xenografts to Patients.MOLECULAR PHARMACEUTICS,15(8),3448-3455.
MLA Liu, Fei,et al."PET Imaging of F-18-(2S,4R)4-Fluoroglutamine Accumulation in Breast Cancer: From Xenografts to Patients".MOLECULAR PHARMACEUTICS 15.8(2018):3448-3455.
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