Neuroendocrine malignant tumors (NET), defined as epithelial neoplasms with predominant neuroendocrine differentiation, arise in most organs of the body. Some of the clinical and pathologic features of these tumors are characteristic of the organ of origin, but other attributes are shared by neuroendocrine neoplasms irrespective of their anatomic site. The multidisciplinary consensus group of experts (North American Neuroendocrine Tumor Society (NANETS), the College of American Pathologists (CAP), the European Neuroendocrine Tumor Society (ENETS)) in the field of NET has recommended a minimum pathology data set of features to be included in pathology reports. The system of classification and nomenclature is depending on the site of the tumor and also of the differentiation grade.

Imaging studies for NET are generally performed for an initial evaluation of the extent of the disease and subsequent follow-up. The goals for the initial evaluation include the identification of the primary tumor, staging, and treatment planning. Subsequent follow-up imaging studies are performed for the surveillance after complete resection or during periods of stability and evaluation of response after the treatment.

Imaging modality commonly used includes the following:

Imaging studies generally recommended at the time of the initial evaluation include plane film radiography of the chest, cross-sectional imaging (CT or MRI) of the abdomen and pelvis, and OctreoScan scintigraphy.

Among patients undergoing surveillance after complete resection, a chest radiography and periodic (every 6–12 months) cross-sectional imaging of the abdomen and pelvis are recommended. For patients having an advanced disease, it is important to evaluate if peptide receptor radionuclide therapy (PRRT) represents a good treatment option.

Imaging is generally performed at 4–6 h and at 24 h. Imaging at 24 or even 48 h provides better contrast because of lower background activity. However, there is often physiological bowel activity that may produce false-positive results. SPECT/CT may be helpful in resolving the nature of indeterminate lesions found on CT and enhances the sensitivity and specificity of the study.

The scintigraphy can be performed for patients on long-acting octreotide but is best performed at the end of the dosing interval (3–6 weeks after the last dose).

For patients on octreotide delivered via a continuous infusion pump or those who received intermittent short-acting octreotide for rescue, it is recommended that these be stopped 48 h before and during testing if possible.

The In-111 octreotide scintigraphy is performed to evaluate the feasibility of PRRT as a scan with intense uptake at all known sites of disease, and it is associated with a higher response rate after radiotherapy with somatostatin receptor targeting.

I-123 MIBG molecular imaging has also been used for NET but has the greatest efficacy in patients with pheochromocytoma, paraganglioma, or neuroblastoma. Some tumors, negative on In-111 octreotide scintigraphy, can be better seen with I-123 MIBG.

Positron emission tomography F18-fluorodeoxyglucose (FDG) imaging, although successful for many solid tumors, has generally not provided additional information about the extent of the disease for well-differentiated NET because of their generally lower proliferative activity.

F18-FDG PET imaging may be used to characterize tumor aggressiveness with higher FDG uptake (expressed as SUV values) having a worse prognosis. This may be helpful when the tumor seems more aggressive than the histology indicates, and additional information for FDG imaging may result in changes of treatment.

Prior studies have shown C11-5-hydroxytryptophan (HTP) PET to be a promising imaging modality for the detection of NET. The serotonin precursor 5-HTP labeled with C-11 was used and showed an increased uptake and irreversible trapping of this tracer in NET. Other new PET imaging agents for NET include F18-DOPA, Ga-68 DOTATOC, Ga-68 DOTANOC, and F18-PGluc-TOCA. In addition, Tc-99m depreotide, which has a greater affinity to somatostatin receptor 3, has also been used for tumor imaging. Although these novel imaging techniques are promising, clinical experiences are limited.

As the latest ESMO guidelines (2012) recommend follow-up, investigations should include biochemical parameters and conventional imaging. In patients with R0/R1 resected NET G1/G2, it is recommended that imaging is performed every 3–6 months (CT or MRI) and, in NEC G3, every 2–3 months. Somatostatin receptor imaging, either OctreoScan or PET/CT using Ga-68 DOTATOC/NOC/TATE, should be included in the follow-up and is recommended after 18–24 months if expression of somatostatin receptor 2A has been proven on the tumor cells. In the case of rapid tumor progression or if imaging information is lacking, it may be necessary to re-biopsy liver metastases to reassess the proliferative activity.