Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total 68Ga-DOTATATE-avid tumor volume measurements

Amit Tirosh, Georgios Z. Papadakis, Corina Millo, Samira M. Sadowski, Peter Herscovitch, Karel Pacak, Stephen J. Marx, Lily Yang, Pavel Nockel, Jasmine Shell, Patience Green, Xavier M. Keutgen, Dhaval Patel, Naris Nilubol, Electron Kebebew*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective: To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by 68Ga DOTATATE PET/CT imaging. Design: 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 total 68Ga-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 with 68Ga-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 and r = 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.

Original languageEnglish
Pages (from-to)575-582
Number of pages8
JournalEuropean Journal of Endocrinology
Issue number5
StatePublished - May 2017


FundersFunder number
National Institute of Child Health and Human DevelopmentZIAHD008735


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