Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT

This bi-centric study aimed to determine the role of receptor PET/CT using Ga-68-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs) and to understand the molecular behaviour of the primarily undiagnosed tumours. Overall 59 patients (33 men and 26 women, age: 65 +/- 9 years) with documented NET and unknown primary were enrolled. PET/CT was performed after injection of approximately 100 MBq (46-260 MBq) of Ga-68-DOTA-NOC. The maximum standardised uptake values (SUVmax) were calculated and compared with SUVmax in known pancreatic NET (pNET) and ileum/jejunum/duodenum (SI-NET). The results of PET/CT were also correlated with CT alone. In 35 of 59 patients (59%), Ga-68-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum/colon (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12 of 59 patients (20%). The mean SUVmax of identified previously unknown pNET and SI-NET were 18.6 +/- 9.8 (range: 7.8-34.8) and 9.1 +/- 6.0 (range: 4.2-27.8), respectively. SUVmax in patients with previously known pNET and SI-NET were 26.1 +/- 14.5 (range: 8.7-42.4) and 11.3 +/- 3.7 (range: 5.6-17.9). The SUVmax of the unknown pNET and SI-NET were significantly lower (p < 0.05) as compared to the ones with known primary tumour sites; 19% of the patients had high-grade and 81% low-grade NET. Based on Ga-68-DOTA-NOC receptor PET/CT, 6 of 59 patients were operated and the primary was removed (4 pancreatic, 1 ileal and 1 rectal tumour) resulting in a management change in approximately 10% of the patients. In the remaining 29 patients, because of the far advanced stage of the disease (due to distant metastases), the primary tumours were not operated. Additional histopathological sampling was available from one patient with bronchial carcinoid (through bronchoscopy). Our data indicate that Ga-68-DOTA-NOC PET/CT is highly superior to In-111-OctreoScan (39% detection rate for CUP according to the literature) and can play a major role in the management of patients with CUP-NET.