Nuclear medicine imaging of gastro-entero-pancreatic neuroendocrine tumors. The key role of cellular differentiation and tumor grade: from theory to clinical practice

Abstract

Nuclear medicine imaging is a powerful diagnostic tool for the management of patients with gastro-entero-pancreatic neuroendocrine tumors, mainly developed considering some cellular characteristics that are specific to the neuroendocrine phenotype. Hence, overexpression of specific trans membrane receptors as well as the cellular ability to take up, accumulate, and decarboxylate amine precursors have been considered for diagnostic radiotracer development. Moreover, the glycolytic metabolism, which is not a specific energetic pathway of neuroendocrine tumors, has been proposed for radionuclide imaging of neuroendocrine tumors. The results of scintigraphic examinations reflect the pathologic features and tumor metabolic properties, allowing the in vivo characterization of the disease. In this article, the influence of both cellular differentiation and tumor grade in the scintigraphic pattern is reviewed according to the literature data. The relationship between nuclear imaging results and prognosis is also discussed. Despite the existence of a relationship between the results of scintigraphic imaging and cellular differentiation, tumor grade and patient outcome, the mechanism explaining the variability of the results needs further investigation.

Figure 1

Results of FDOPA PET (A,C) and SRS (B,E) performed in a 56-year-old patient presenting hepatic metastases (D) of a well-differentiated NET of unknown origin (Ki-67, 5%). SRS allowed the visualization of multiple foci of pathologic uptake in the liver, lymph nodes and bones without evidence of the primary tumor. FDOPA PET confirmed massive bone marrow and skeletal involvement, as well as multiple lymphatic and hepatic metastases. Moreover, FDOPA PET demonstrated intense and focal uptake in the head of pancreas (arrowhead), later confirmed as the primary tumor.

Figure 2

FDG (A,C) and FDOPA PET/CT (B,E) results performed before liver transplantation in a 49-year-old patient with a history of well-differentiated ileal NET surgically treated (Ki-67, 1%). Intense uptake of FDOPA was observed in multiple and voluminous hepatic metastases. FDG PET showed no or minimal uptake in the liver lesions.

Figure 3

Results of FDG PET (A,C), SRS-SPECT (B,E) and corresponding non-enhanced CT slice (D) performed in a 63-year-old patient with poorly differentiated rectal NET (Ki-67, 11%). FDG PET allowed the detection of the primary tumor and both lymphatic para-aortic and right-lobe hepatic metastases. On the other hand, SRS showed no pathologic uptake, particularly in the liver (arrowheads).

Figure 4

SRS (A), FDOPA (B,D) and FDG PET/CT (C,F) results performed for restaging purposes in a 66-year-old patient with a history of well-differentiated colic NET (Ki-67, 2%) previously treated by surgery. SRS only showed faint uptake concerning a peritoneal relapse (*). FDOPA PET showed a clear multifocal peritoneal carcinomatosis (arrowhead) and multiple hepatic metastases. Despite the absence of focal FDG uptake, diffuse and moderate uptake was observed in the pelvic cavity suggesting the shield sign, in keeping with peritoneal carcinomatosis.

Figure 5

Multiple hepatic metastases (C,D, contrast-enhanced CT maximum projection intensity and axial slice performed some days after the scintigraphic examinations) in a 57-year-old patient with poorly differentiated pancreatic NET previously treated by surgery. Biopsy confirmed the neuroendocrine nature of one hepatic lesion. The pathologic report showed a well-differentiated NET (Ki-67, <3%). Several hepatic foci of pathologic uptake were detected by FDG PET (A) and SRS (B). Some lesions showed both radiotracer uptake and other exclusive uptake of FDG or labeled somatostatin analogs (arrowhead). The discrepancy between the results of pathologic reports and isotopic procedures strongly suggests different degrees of tumor differentiation in the same patient.

Figure 6

FDOPA PET (A,D), FDG PET (B,F) and enhanced CT (C,E) results of a 65-year-old patient with a duodenal NET and liver metastatic involvement. Biopsy of one hepatic localization showed a well-differentiated carcinoma with Ki-67 index of 10%. The pathologic examination of the primary tumor showed poorly differentiated carcinoma with a Ki-67 index of 10%. Both FDG PET and FDOPA PET showed multiple non-concordant foci of pathologic uptake in the liver (arrowheads).

Figure 7

FDG PET (A,C) and FDOPA PET (B,E) results for a 68-year-old patient with clinical and biological suspicion of NET. FDG PET showed an exclusive pathologic uptake in hepatic segment IV–VIII, corresponding to a metastatic lesion on enhanced CT (D). Biopsy of hepatic metastasis (arrowheads) showed a well-differentiated NET of unknown origin with a Ki-67 index of 3%. FDOPA PET showed the ileal primary tumor (*) and multiple hepatic and lymph node metastases.