title: Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma.
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 (SUV(max)) of FDG or FDOPA by the primary tumor. Patients with older age, advanced stages, or MYCN amplification showed higher FDG and lower FDOPA SUV(max) (all P < 0.02). Receiver operating characteristics analysis identified FDG SUV(max) ≥ 3.31 and FDOPA SUV(max) < 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 SUV(max) (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.
authors.affiliation: Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan.|PhD Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan.|Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.|Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Meng-Yao
authors.initials: MY
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsiu-Hao
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ching-Chu
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Dong-Tsamn
authors.initials: DT
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shiann-Tarng
authors.initials: ST
authors.lastname: Jou
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yung-Li
authors.initials: YL
authors.lastname: Yang
authors.affiliation: Department of Nursing, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Shiu-Feng
authors.initials: SF
authors.lastname: Huang
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.affiliation: Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.|College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: James S
authors.initials: JS
authors.lastname: Miser
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Liao
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.affiliation: Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Molecular Imaging Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Tzen
mesh_terms: D015331:Cohort Studies; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000032:analysis* / Q000493:pharmacokinetics; D023281:Genomics; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000032:analysis* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine
keywords: FDG; FDOPA; copy number alterations; neuroblastoma; positron emission tomography