Metabolic Evaluation of MYCN-Amplified Neuroblastoma by 4-[F-18]FGln PET Imaging

doi:10.1007/s11307-019-01330-9

	Metabolic Evaluation of MYCN-Amplified Neuroblastoma by 4-[F-18]FGln PET Imaging
	Li, Chao 1; Huang, Shuo 1; Guo, Jun 1; Wang, Cheng 6; Huang, Zhichao 2; Huang, Ruimin 3,4; Liu, Liang 5; Liang, Sheng 1; Wang, Hui 1
刊名	MOLECULAR IMAGING AND BIOLOGY
	2019-12-01
卷号	21 期号:6 页码:1117-1126
关键词	Glutamine PET MYCN ASCT2 Neuroblastoma
ISSN号	1536-1632
DOI	10.1007/s11307-019-01330-9
通讯作者	Huang, Shuo(rmhuang@simm.ac.cn) ; Liang, Sheng(liangsheng364214@163.com) ; Wang, Hui(wanghui@xinhuamed.com.cn)
英文摘要	Purpose This study aims to explore whether 4-(2S,4R)-[F-18]fluoroglutamine (4-[F-18]FGln) positron emission tomography (PET) imaging is helpful in identifying and monitoring MYCN-amplified neuroblastoma by enhanced glutamine metabolism. Procedures Cell uptake studies and dynamic small-animal PET studies of 4-[F-18]FGln and 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) were conducted in human MYCN-amplified (IMR-32 and SK-N-BE (2) cells) and non-MYCN-amplified (SH-SY5Y cell) neuroblastoma cells and animal models. Subsequently, short hairpin RNA (shRNA) knockdown of alanine-serine-cysteine transporter 2 (ASCT2/SLC1A5) in IMR-32 cells and xenografts were investigated in vitro and in vivo. Western blot (WB), real-time polymerase chain reaction (RT-PCR), and immunofluorescence (IF) assays were used to measure the prevalence of ASCT2, Ki-67, and c-Caspase 3, respectively. Results IMR-32 and SK-N-BE (2) cells showed high glutamine uptake in vitro (31.6 +/- 1.7 and 21.6 +/- 6.6 %ID/100 mu g). In the in vivo study, 4-[F-18]FGln was localized in IMR-32, SK-N-BE (2), and SH-SY5Y tumors with a high uptake (6.6 +/- 0.3, 5.6 +/- 0.2, and 3.7 +/- 0.1 %ID/g). The maximum uptake (tumor-to-muscle, T/M) of the IMR-32 and SK-N-BE (2) tumors (3.71 and 2.63) was significantly higher than that of SH-SY5Y (1.54) tumors (P < 0.001, P < 0.001). The maximum uptake of 4-[F-18]FGln in IMR-32 and SK-N-BE (2) tumors was 2.3-fold and 2.1-fold higher than that of [F-18]FDG, respectively. Furthermore, in the in vitro and in vivo studies, the maximum uptake of 4-[F-18]FGln in shASCT2-IMR-32 cells and tumors was 2.1-fold and 2.5-fold lower than that of the shControl-IMR-32. No significant difference in [F-18]FDG uptake was found between shASCT2-IMR-32 and shControl-IMR-32 cells and tumors. Conclusion 4-[F-18]FGln PET can provide a valuable clinical tool in the assessment of metabolic glutamine uptake in MYCN-amplified neuroblastoma. ASCT2-targeted therapy may provide a supplementary method in MYCN-amplified neuroblastoma treatment.
WOS关键词	GLUTAMINE-METABOLISM ; CANCER ; ASCT2 ; EXPRESSION ; ACID ; TRANSPORT ; LAT1 ; ATF4
WOS研究方向	Radiology, Nuclear Medicine & Medical Imaging
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000497304600013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282008]
专题	中国科学院上海药物研究所
通讯作者	Huang, Shuo; Liang, Sheng; Wang, Hui
作者单位	1.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Nucl Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China 2.PINGSENG Healthcare, 999 Qujia Rd, Kunshan 215341, Jiangsu, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 5.Shanghai Jiao Tong Univ, Dept Cardiol, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China 6.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Nucl Med, 1630 Dongfang Rd, Shanghai 200127, Peoples R China
推荐引用方式 GB/T 7714	Li, Chao,Huang, Shuo,Guo, Jun,et al. Metabolic Evaluation of MYCN-Amplified Neuroblastoma by 4-[F-18]FGln PET Imaging[J]. MOLECULAR IMAGING AND BIOLOGY,2019,21(6):1117-1126.
APA	Li, Chao.,Huang, Shuo.,Guo, Jun.,Wang, Cheng.,Huang, Zhichao.,...&Wang, Hui.(2019).Metabolic Evaluation of MYCN-Amplified Neuroblastoma by 4-[F-18]FGln PET Imaging.MOLECULAR IMAGING AND BIOLOGY,21(6),1117-1126.
MLA	Li, Chao,et al."Metabolic Evaluation of MYCN-Amplified Neuroblastoma by 4-[F-18]FGln PET Imaging".MOLECULAR IMAGING AND BIOLOGY 21.6(2019):1117-1126.