Prospective Study of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic Neuroendocrine Tumors and Unknown Primary Sites

Abstract

Purpose: Gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) are increasing in incidence, and accurate staging is important for selecting the appropriate treatment. (68)Ga-DOTATATE imaging is a promising approach for detecting GEPNETs and could help in selecting optimal therapeutic strategies. The aim of this study was to prospectively determine the clinical utility of (68)Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) in detecting unknown primary and metastatic GEPNETs.

Patients and methods: One hundred thirty-one patients were enrolled in a prospective study of patients undergoing (68)Ga-DOTATATE PET/CT, (111)In-pentetreotide single-photon emission computed tomography (SPECT)/CT and multiphasic CT scan, and/or magnetic resonance imaging in a blinded fashion with comprehensive biochemical testing. The primary outcome measure was the detection of lesions by each imaging study.

Results: (68)Ga-DOTATATE PET/CT imaging detected 95.1% of lesions (95% CI, 92.4% to 96.8%) with an average maximum standardized uptake value of 65.4 ± 47 (range, 6.9 to 244), anatomic imaging detected 45.3% of lesions (95% CI, 37.9% to 52.9%), and (111)In-pentetreotide SPECT/CT detected 30.9% of lesions (95% CI, 25.0% to 37.5%), with a significant difference between imaging modalities (P < .001). In four of 14 patients (28.6%), (68)Ga-DOTATATE PET/CT found a previously unknown primary tumor, and detected primary GEPNET, lymph node, and distant metastases correctly in 72 of 113 lesions (63.7%) when compared with histopathology, with 22.1% and 38.9% detected by using (111)In-pentetreotide SPECT/CT and anatomic imaging, respectively. On the basis of findings with (68)Ga-DOTATATE PET/CT, 43 of 131 patients (32.8%) had a change in management recommendation. In patients with carcinoid symptoms but negative biochemical testing, (68)Ga-DOTATATE PET/CT detected lesions in 65.2% of patients, 40% of which were detected neither by anatomic imaging nor by (111)In-pentetreotide SPECT/CT.

Conclusion: (68)Ga-DOTATATE PET/CT imaging provides important information for accurate staging of GEPNETs and selection of appropriate treatment interventions even in the absence of biochemical evidence of disease in symptomatic patients.

Fig 1.

There was a significant correlation between (A) chromogranin A and (B) 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) and the number of lesions per patient found by using ⁶⁸Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) imaging (Spearman coefficient r = 0.46; P < .001; n = 128; and r = 0.43; P < .001; n = 119, respectively). Mean (C) chromogranin A and (D) 24-hour urinary 5-HIAA were significantly higher in patients with liver metastases present with ⁶⁸Ga-DOTATATE PET/CT imaging (chromogranin A: liver positive [pos] 1083 ± 446 v liver negative [neg] 356 ± 104; Mann-Whitney P = .005; and 5-HIAA: liver positive 20 ± 5.8 v liver negative 4.7 ± 0.3; Mann-Whitney P < .001).

Fig 2.

A case of a patient with known liver metastases and previously unknown primary lesion detected by ⁶⁸Ga-DOTATATE positive emission tomography (PET)/computed tomography (CT). (A) ¹¹¹In-Pentetreotide scan (planar) shows no pathologic uptake. (B, top) Axial CT, (middle) ¹¹¹In-pentetreotide axial slice, and (bottom) fused single-photon emission CT/CT showing no pathologic uptake. (C) ⁶⁸Ga-DOTATATE PET maximum-intensity projection image shows three liver metastases (black arrows) and two lesions in the abdomen (lymph node and enteric lesion; red arrows). (D) ⁶⁸Ga-DOTATATE PET/CT image shows the mesenteric lymph node (maximum standardized uptake value, 75; red arrow). (E) Arterial phase CT shows corresponding small indeterminate lymph node (red arrow).

Fig 3.

Clinical management diagram on the basis of the three imaging modalities. Data are given as No. (%). CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; PRRT, peptide receptor radionuclide therapy; SPECT, single-photon emission computed tomography.

Fig A1.

A 46-year-old patient with multiple endocrine neoplasia type 1 and known pancreatic and duodenal lesions who had lymph nodes not previously known that were detected by using ⁶⁸Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) imaging. (A) ¹¹¹In-Pentetreotide scan (planar) shows a unique unclear prerenal uptake. (B, top) Axial CT, (middle) ¹¹¹In-pentetreotide axial slice, and (bottom) fused single-photo emission CT/CT showing unclear pathologic uptake (red arrow). (C) ⁶⁸Ga-DOTATATE PET maximum-intensity projection image shows retropancreatic lymph node (red arrow) and duodenal and pancreatic lesions. (D) ⁶⁸Ga-DOTATATE Q:17 PET/CT image shows the retropancreatic and periduodenal lymph node (maximum standardized uptake value, 96; red arrow). (E) Arterial phase CT shows corresponding lymph node (red arrow) that was read as a subcentimeter indeterminate lymph node.