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

Abstract

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 (68)Ga-labeled somatostatin analogs ((68)Ga-DOTA-SSTa) and (18)F-DOPA have shown promise. In direct comparisons between (68)Ga-DOTA-SSTa PET/CT and (99m)Tc-HYNIC-octreotide/(111)In-pentetreotide SPECT(/CT), (68)Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. (18)F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of (18)F-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 (68)Ga-DOTA-SSTa, alternatively (18)F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and (18)F-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.

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

“…111 In-pentetreotide (Octreoscan) has been widely used for NET imaging, but is limited by its low image resolution and long scan duration and relatively lower SSTRs affinity[8]. In contrast, the 68 -Gallium ( 68 Ga)-DOTA-compounds recently introduced into clinical practice ( 68 Ga-DOTATATE, 68 Ga-DOTANOC, 68 Ga-DOTATOC), have been shown to have higher sensitivity for detecting NET than Octreoscan[9] and significantly impact the management of patients with NET [10,11].…”

68Ga-TRAP-(RGD)3 Hybrid Imaging for the In Vivo Monitoring of αvß3-Integrin Expression as Biomarker of Anti-Angiogenic Therapy Effects in Experimental Breast Cancer

“…While 18 F-fluorodeoxyglucose (FDG) remains the most widely applied tracer in positron emission tomography (PET), the arsenal of diagnostic radiotracers has been expanded significantly over the last decade [2–5]. The development of radiolabeled arginylglycylaspartic acid (RGD) tracers has enabled the specific targeting of α v ß 3 -integrin, an endothelial and tumor cell receptor with a significant role in neoangiogenesis [6].…”

ENETS Consensus Recommendations for the Standards of Care in Neuroendocrine Neoplasms: Follow-Up and Documentation

“…Currently, there are only limited data available of PET-based imaging for routine follow-up, and its significance in this respect is currently not possible to define. However, PET may reveal metastases not seen on SRS or CT, particularly in bone and lymph nodes [30,31,[33][34][35] . Grade uptake at SRI as well as homogeneity of uptake should be specified [38] , also to evaluate the eligibility for peptide receptor radionuclide treatment.…”