Both anatomical and functional imaging techniques are important for the workup of NETs. Typically, the initial and most common evaluation is by contrast-enhanced CT of the chest, abdomen, and pelvis, which is used to try and identify the primary tumor as well as metastases. While CT has many strengths, its weaknesses for visualizing NETs are a lack of sensitivity in the liver and its high dependency on the timing of the contrast injection. A CT scan is usually not diagnostic of the FULL EXTENT OF DISEASE. Most liver metastases only appear in the arterial phases when contrast is used. A non-contrast study may miss all but the largest liver metastases. A more sensitive test for the liver and bone is MRI. With liver specific contrast, it can detect up to 20% more disease. Diffusion weighted protocols are particularly sensitive as NETs have a unique water pattern in relationship to the normal liver parenchyma. Endoscopic procedures including endoscopic ultrasound can be useful in identifying gastrointestinal NETs.
A comparison in the same patient between a In111-pentetreotide scan (OctreoScan, left) and Ga68-DOTATATE PET (NetSpot, right). Images courtesy of Hong Song, MD, PhD (Stanford University).
Functional (nuclear) imaging also has an important role in diagnosing NETs by utilizing the expression of somatostatin receptors (SSTRs) to identify tumor sites. This technology has been available for many decades with gamma-camera imaging or single photon emission computed tomography (SPECT), using the radiopharmaceutical 111-Indium-pentreotide (OctreoScan), which has limited resolution, but the tracer and the scanner are widely available. Since 2016, a newer generation radiopharmaceutical 68-Gallium-DOTATATE(NETSPOT®) has been FDA-approved for this same indication, using positron emission tomography (PET) coupled with CT or MRI. It has many advantages over an OctreoScan, including much higher resolution, better sensitivity, a shorter scan time and a lower radiation dose. Where the 68Ga-DOTATATE scan is available, it is the much preferred scan for visualizing extent of disease. There remain issues with access and insurance approvals for this scan though this is decreasing. Recently, Appropriate Use Criteria for 68Ga-DOTATATE were published in the Journal of Nuclear Medicine; in brief, SSTRimaging has a role in diagnosis, identification of the primary, staging, restaging and selection of patients for peptide receptor radionuclide therapy (PRRT) with 177-Lutetium-DOTATATE (LUTATHERA®). Its role in assessment of response to treatment remains under investigation. In general, SSTR-imaging is most effective for well differentiated tumors, since poorly differentiated tumors may not express SSTRs at a sufficiently high concentration. For patients with NECs and some with Grade 3 NETs the standard PET radiopharmaceutical 18F-fluorodeoxyglucose (FDG) is preferred. For tumors with a proliferation index in the middle-ground, Ki67 of 20-55%, both 68Ga-DOTATATE and FDG PET may be required for full staging.
