title: Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total68Ga-DOTATATE-Avid tumor volume measurements.
abstract: OBJECTIVE
  To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by68Ga DOTATATE PET/CT imaging.
  
  
  METHODS
  A retrospective analysis of a prospective database of patients with NETs.
  
  
  METHODS
  Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total68Ga-DOTATATE-avid tumor volume (TV) was analyzed.
  
  
  RESULTS
  The analysis included 232 patients. In patients with pancreatic NETs (n= 112),68Ga-DOTATATE TV correlated with CgA (r= 0.6,P= 0.001, Spearman). In patients with multiple endocrine neoplasia type 1 (n= 39),68Ga-DOTATATE TV correlated with glucagon (r= 0.5,P= 0.01) and PP levels (r= 0.5,P= 0.049). In patients with von Hippel-Lindau (n= 24), plasma VIP (r= 0.5,P= 0.02) and PP levels (r= 0.7,P< 0.001) correlated with68Ga-DOTATATE TV. In patients with small intestine NET (SINET,n= 74),68Ga-DOTATATE TV correlated with CgA (r= 0.5,P= 0.02) and 5-HIAA levels (r= 0.7,P< 0.001), with 5-HIAA ≥8.1 mg/24 h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values (P= 0.001).68Ga-DOTATATE TV in patients with NET of unknown primary (n= 16) and those with NET of other primary location (n= 30) correlated with 5-HIAA levels (r= 0.8,P= 0.002 andr= 0.7,P= 0.02 respectively).
  
  
  CONCLUSIONS
  Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.
authors.affiliation: Section on Medical NeuroendocrinologyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.|Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Tirosh
authors.affiliation: PET-DepartmentNational Institutes of Health Clinical Center, Bethesda, Maryland, USA.|Institute of Computer Science (ICS)Foundation for Research and Technology Hellas (FORTH), Crete, Greece.
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Papadakis
authors.affiliation: PET-DepartmentNational Institutes of Health Clinical Center, Bethesda, Maryland, USA.
authors.forename: Corina
authors.initials: C
authors.lastname: Millo
authors.affiliation: Endocrine and Thoracic SurgeryUniversity Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Samira M
authors.initials: SM
authors.lastname: Sadowski
authors.affiliation: PET-DepartmentNational Institutes of Health Clinical Center, Bethesda, Maryland, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.affiliation: Section on Medical NeuroendocrinologyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.affiliation: Section on Medical NeuroendocrinologyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Marx
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Nockel
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Shell
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Patience
authors.initials: P
authors.lastname: Green
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.|Department of SurgeryRush University Medical Center, Chicago, Illinois, USA.
authors.forename: Xavier M
authors.initials: XM
authors.lastname: Keutgen
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dhaval
authors.initials: D
authors.lastname: Patel
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.affiliation: Endocrine Oncology BranchNational Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.|Department of SurgeryThe George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia, USA.
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging; D009377:Multiple Endocrine Neoplasia / Q000000981:diagnostic imaging / Q000378:metabolism; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009942:Organometallic Compounds; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D006897:Hydroxyindoleacetic Acid; C513399:gallium Ga 68 dotatate