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Mol Imaging Biol. 2019 Mar 8. doi: 10.1007/s11307-019-01330-9. [Epub ahead of print]

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

Author information

1
Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
2
Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, 1630 Dongfang Road, Shanghai, 200127, China.
3
PINGSENG Healthcare, 999 Qujia Road, Kunshan, 215341, Jiangsu, China.
4
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China. rmhuang@simm.ac.cn.
5
University of Chinese Academy of Sciences, No.19(A) Yuquan Road, Beijing, 100049, China. rmhuang@simm.ac.cn.
6
Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
7
Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. liangsheng364214@163.com.
8
Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. wanghui@xinhuamed.com.cn.

Abstract

PURPOSE:

This study aims to explore whether 4-(2S,4R)-[18F]fluoroglutamine (4-[18F]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-[18F]FGln and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]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 μg). In the in vivo study, 4-[18F]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-[18F]FGln in IMR-32 and SK-N-BE (2) tumors was 2.3-fold and 2.1-fold higher than that of [18F]FDG, respectively. Furthermore, in the in vitro and in vivo studies, the maximum uptake of 4-[18F]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 [18F]FDG uptake was found between shASCT2-IMR-32 and shControl-IMR-32 cells and tumors.

CONCLUSION:

4-[18F]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.

KEYWORDS:

ASCT2; Glutamine; MYCN; Neuroblastoma; PET

PMID:
30850970
DOI:
10.1007/s11307-019-01330-9

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