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Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma

Yen-Lin Liu, Meng-Yao Lu, Hsiu-Hao Chang, Ching-Chu Lu, Dong-Tsamn Lin, Shiann-Tarng Jou, Yung-Li Yang, Ya-Ling Lee, Shiu-Feng Huang, Yung-Ming Jeng, Hsinyu Lee, James S. Miser, Kai-Hsin Lin, Yung-Feng Liao, Wen-Ming Hsu and Kai-Yuan Tzen _

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Oncotarget. 2016; 7:18774-18786. https://doi.org/10.18632/oncotarget.7933

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Abstract

Yen-Lin Liu1,2,3,4,5,*, Meng-Yao Lu4,*, Hsiu-Hao Chang4, Ching-Chu Lu6, Dong-Tsamn Lin4,7, Shiann-Tarng Jou4, Yung-Li Yang4,7, Ya-Ling Lee8, Shiu-Feng Huang9, Yung-Ming Jeng10, Hsinyu Lee11, James S. Miser5,12, Kai-Hsin Lin4, Yung-Feng Liao3, Wen-Ming Hsu13,14, Kai-Yuan Tzen6,15

1Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan

2PhD Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan

3Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

4Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

5Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan

6Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

7Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

8Department of Nursing, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

9Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan

10Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

11Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan

12College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

13Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

14Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan

15Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

*These authors contributed equally to this work

Correspondence to:

Kai-Yuan Tzen, e-mail: tzenky@ntu.edu.tw

Wen-Ming Hsu, e-mail: billwmhsu@gmail.com

Keywords: neuroblastoma, positron emission tomography, FDG, FDOPA, copy number alterations

Received: November 02, 2015     Accepted: February 11, 2016     Published: March 05, 2016

ABSTRACT

Neuroblastoma (NB) is a heterogeneous childhood cancer that requires multiple imaging modalities for accurate staging and surveillances. This study aims to investigate the utility of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluoro-dihydroxyphenylalanine (FDOPA) in determining the prognosis of NB. During 2007–2014, forty-two NB patients (male:female, 28:14; median age, 2.0 years) undergoing paired FDG and FDOPA PET scans at diagnosis were evaluated for the maximum standardized uptake value (SUVmax) of FDG or FDOPA by the primary tumor. Patients with older age, advanced stages, or MYCN amplification showed higher FDG and lower FDOPA SUVmax (all P < 0.02). Receiver operating characteristics analysis identified FDG SUVmax≥ 3.31 and FDOPA SUVmax < 4.12 as an ultra-high-risk feature (PET-UHR) that distinguished the most unfavorable genomic types, i.e. segmental chromosomal alterations and/or MYCN amplification, at a sensitivity of 81.3% (54.4%–96.0%) and a specificity of 93.3% (68.1%–99.8%). Considering with age, stage, MYCN status, and anatomical image-defined risk factor, PET-UHR was an independent predictor of inferior event-free survival (multivariate hazard ratio, 4.9 [1.9–30.1]; P = 0.012). Meanwhile, the ratio between FDG and FDOPA SUVmax (G:D) correlated positively with HK2 (Spearman’s ρ = 0.86, P < 0.0001) and negatively with DDC (ρ = −0.58, P = 0.02) gene expression levels, which might suggest higher glycolytic activity and less catecholaminergic differentiation in NB tumors taking up higher FDG and lower FDOPA. In conclusion, the intensity of FDG and FDOPA uptake on diagnostic PET scans may predict the tumor behavior and complement the current risk stratification systems of NB.


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