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

Abstract

Objective To determine the association between neuroendocrine tumor (NET) biomarker levels and 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-hour 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=0.02) 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/24h 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.

PET/CT and PET/MRI in ophthalmic oncology (Review)

“…Bone FD has been visualized with conventional SSTRs scintigraphy using 111 ln-pentetreotide, suggesting cell surface over-expression of SSTRs by fibrous dysplastic cells (119). The introduction of 68 Ga-DOTA-conjugated-peptides into clinical practice has enabled the employment of PET-imaging in targeting lesions, characterized by SSTRs-overexpressi on (18,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Papadakis et al reported intensely increased 68 Ga-DOTATE (radiolabeled somatostatin analogue suitable for PET-imaging, which targets SSTRs) activity on PET/CT, by a biopsy proven FD lesion in the temporal bone (22).…”

“…68 Ga-DOTA-compounds are somatostatin (SST) analogs, radiolabeled with the positron emitting isotope gallium-68 ( 68 Ga) through the chelator 1,4,7,10-tetraazacyclododecane-1, 4,7,10-tetraacetic acid (DOTA) (18). The employment of these compounds enables highly efficient targeting of lesions which are characterized by cell-surface over-expression of SST receptors (SSTRs), such as neuroendocrine tumors (NETs), for which PET/CT imaging with 68 Ga-DOTA-compounds is evolving as the imaging standard of reference (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33).…”

Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site

“…Secretion of chromogranin A into blood is fairly ubiquitous across NENs [34] and is therefore unlikely to be of assistance in determining the primary site once a histological diagnosis is made. 24-h urinary 5-hydroxyindoleacetic acid, a break-down product of serotonin is more commonly raised in small intestinal NENs with high levels associated with metastatic disease [35].…”

Functional Imaging of Paragangliomas with an Emphasis on Von Hippel–Lindau-Associated Disease: A Mini Review

“…Furthermore, false positives may be expected in metastatic lymph nodes, meningiomas, and inflammation foci ( 21 ). Recently, novel 68 Gallium ( 68 Ga)-DOTA-labeled somatostatin analogs ( 68 Ga-DOTATATE, 68 Ga-DOTANOC, and 68 Ga-DOTATOC) have been introduced to clinical PET/CT use; they are reported to have higher sensitivity for detecting neuroendocrine tumors compared to “classic” SRS ( 25 ) ( Figure 1 ). 68 Ga-DOTATATE PET/CT was better than 18 F-DOPA, 18 F-FDA PET/CT, CT/MRI, and especially 18 F-FDG PET/CT in imaging patients ( n = 22) with sporadic metastatic PHEO/PGL ( 26 ), or head and neck PGLs (sensitivity reported at 93% in a series of 30 patients) ( 20 ).…”