Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

Prasanna Santhanam, Sangeeta Chandramahanti, Alexander Kroiss, Run Yu, Philippe Ruszniewski, Rakesh Kumar, David Taïeb

Research output: Contribution to journalReview articlepeer-review


Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22 %), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as 68Ga-labeled somatostatin analogs (68Ga-DOTA-SSTa) and 18F-DOPA have shown promise. In direct comparisons between 68Ga-DOTA-SSTa PET/CT and 99mTc-HYNIC-octreotide/111In-pentetreotide SPECT(/CT), 68Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. 18F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of 18F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with 68Ga-DOTA-SSTa, alternatively 18F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and 18F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly developed PET approaches (radiopharmaceuticals) and intraoperative PET imaging.

Original languageEnglish (US)
Pages (from-to)1144-1155
Number of pages12
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number7
StatePublished - Jun 1 2015


  • F-DOPA
  • Gallium radioisotopes
  • Neuroendocrine tumors
  • Positron emission tomography
  • Somatostatin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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