Gastroenteropancreatic NETs comprise a significant proportion of well-differentiated NETs. Midgut NETs, formerly known as carcinoid tumors, represent the most common subtype of advanced, well-differentiated, gastroenteropancreatic NETs. They often secrete serotonin and other vasoactive substances, and they can cause carcinoid syndrome, which is associated with symptoms such as flushing and diarrhea. Although there are exceptions, there is a correlation between tumor burden and carcinoid syndrome. The standard first-line treatment for metastatic unresectable NETs with carcinoid syndrome is a somatostatin analogue, for both control of the syndrome and stabilization of tumor growth. 

Well-differentiated, functional, small bowel NETs typically express SSTRs, whereas SSTR negativity often correlates with higher-grade, more aggressive NETs. A higher degree of SSTR expression on SSTR imaging is, to some extent, predictive of a patient’s response to peptide receptor radionuclide therapy (PRRT).

Some well-differentiated tumors may have absent/poor SSTR expression or heterogeneous SSTR expression. SSTR-negative tumors tend to be more aggressive and can potentially be avid on a fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) PET. This is often referred to as discordance, when a tumor may be FDG positive and SSTR negative. Discordant tumors that are SSTR negative and FDG positive are often a higher grade or more aggressive. However, it is not always necessary to obtain an FDG PET in these cases, since tumor growth is often observable on conventional anatomic imaging. 

The current guidelines from the North American Neuroendocrine Tumor Society include recommendations on the use of SSTR PET imaging and PRRT in the treatment of NETs. In the NETTER-1 study with lutetium-177–DOTATATE, patients had a well-differentiated histology with a Ki-67 proliferative index of 20% or less and positive uptake on SSTR scintigraphy. Since that time, DOTATATE PET/computed tomography (CT) emerged. In candidates for PRRT, we generally like to see an SSTR expression level in the tumors that is higher than that of the liver on gallium-68 (⁶⁸Ga)–DOTATATE or copper-64 (⁶⁴Cu)–DOTATATE PET/CT imaging. It is important to try to evaluate all measurable tumors for SSTR expression with our colleagues in nuclear medicine. PRRT can be an option when tumors are DOTATATE PET positive and FDG PET positive, but, if tumors are DOTATATE PET negative or weakly positive, then that patient is probably not an appropriate candidate for PRRT.

SSTR PET imaging may also be useful in the evaluation of the primary tumor. The question of whether to surgically remove the primary tumor in asymptomatic patients with inoperable metastatic liver disease has been ongoing for decades; the absence of randomized data makes it very difficult to analyze. If the primary tumor is symptomatic, then it almost certainly should be removed. It should also be resected if the patient is asymptomatic but appears to be at risk for bowel obstruction. The potential for obstruction is also a consideration with PRRT. For instance, you could have a mesenteric lymph node that is tethering the bowel, or peritoneal carcinomatosis, that could lead to bowel obstruction with PRRT.