The Supporting Role of (18)FDG-PET in Patients with Neuroendocrine Tumors.

Abstract

There has been a marked, unexplained increasing incidence of neuroendocrine tumors (NETs) over the past few decades. This may be due to a combination of different factors, such as changes in the environment with new exposures to injurious agents or an increased awareness of these neoplasms, but perhaps most of all, improvements in and utilization of body imaging. It has been estimated that as many as 72 million computed tomographic (CT) scans are done per year in the United States, a threefold increase since 1993. Abdominal CTs will detect liver metastases, and metastatic disease is found in 30 % of patients with small bowel NETs and 64 % of those with pancreatic NETs. Primary pancreatic NETs are commonly seen on CT if they are greater than 1 cm in size and appropriate administration of intravenous contrast is given. Primary small bowel NETs are more subtle because they are frequently small and intramural. They may show up as thickening of the bowel wall or a mass, but more commonly, one may see enlarged, calcified nodes in the mesentery. Although anatomic imaging (CT, MRI) has been very useful, the finding of a mass in the pancreas, mesentery, or liver does not define a tumor as being neuroendocrine in origin. This is where functional imaging for NETs can be useful. For these studies, octreotide is conjugated to a radioisotope, which accumulates in areas with a high density of somatostatin type 2 (SST2) receptors, which are expressed on the cell membranes of the majority of NETs. This has evolved into the exam we know today as OctreoScan, where patients are given an intravenous injection of In-octreotide, and then scintigraphy is performed at 4 and 24 h. One important early study optimistically quoted finding uptake in 96 % of small bowel and 68 % of pancreatic NETs, but never specified whether the uptake seen was in primary tumors or their metastases. Nevertheless, this imaging modality has turned out to be useful in NETs from a multitude of primary sites, as long as they express SST2 receptors. Improvements have come over time with the administration of a bowel preparation before imaging, combining with single-photon emission computed tomography (SPECT), and more recently, by coregistration with CT scans. One recent study evaluating OctreoScans in patients with surgically confirmed small bowel NETs found that either the primary tumor or adjacent nodes had uptake in 74 % of cases, and liver metastases in 66 % (of cases where metastases were present). Functional imaging for NETs has used other agents over the years, including I-Tyr-octreotide and I-MIBG, in addition to the standard of In-octreotide. A more contemporary improvement has come from combining functional imaging with positron emission tomography (PET). The advantage of PET over SPECT is that the latter relies on detection of single photons, which are emitted in all directions. In PET, the decay of a positron causes the emission of two photons in opposite directions, which allows for significant improvement in resolution and precise quantitative imaging. The most useful scans for patients with NETs have been a PET scan using the positron emitter Ga conjugated to DOTA-modified octreotide (DOTATATE or DOTATOC). Imaging can be done with less radiation exposure, and in just 1 h instead of 2 days with significantly improved resolution as compared to OctreoScan. In addition, like OctreoScan, it helps to predict those likely to respond to peptide radioreceptor therapy for these tumors. Although widely available in Europe for the last decade, there have been barriers to its use and adoption in the United States because it is not Society of Surgical Oncology 2015