8Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours
Introduction
Neuroendocrine tumours (NETs) have unique properties that are important to consider for radiological and nuclear medicine imaging. NETs arise from the cells of the diffuse endocrine system of specialised cells with different function and hormonal production which give rise to a heterogeneous group of tumours with very variable clinical expression [1], ∗[2]. NETs are most frequent in the gastro-intestinal and broncho-pulmonary system. The NET incidence is approximately 5/100 000 per year but the prevalence is much higher, 35/100 000 per year [3].
A NET may be functioning and give rise to hormonal symptoms or it can be non-functioning, although hormonal production from non-functioning NETs may sometimes be shown biochemically. Small bowel NETs generally produce serotonin and functioning pancreatic NETs (pNETs), arising from the islets of Langerhan, produce hormones according to its cell of origin (insulin, glucagon, gastrin, vasointestinal peptide etc.). The vast majority of NETs are slow growing with low proliferation (ki-67 index ≤2%, G1 tumours) and express somatostatin receptors, which forms the basis for somatostatin receptor imaging (SRI) and for therapy. A minor part of NETs have higher proliferation and a clinically more aggressive behaviour (ki-67 index 3–20%, G2) and rarely poorly differentiated neuroendocrine carcinoma (ki-67 index >20%, G3).
Many patients, typically those with small bowel NETs, present with vague diffuse unspecific symptoms. There are therefore often years of both patient's and doctor's delay and approximately half of the patients have disseminated disease at the time of diagnosis. The functioning pNETs can, by contrast, give rise to pronounced hormonal symptoms although the tumour is very small. The non-functioning pNETs usually give rise to abdominal discomfort and pain and often are fairly large at diagnosis.
Because of these very varying tumour properties and clinical behaviour, the presentation of the disease in the individual patients is very diverse. Consequently, the need for imaging varies considerably between patients [4], ∗[5].
The only curative treatment of NET is surgical resection. Surgery is also a means for tumour debulking to decrease hormonal symptoms and for management of locoregional symptoms. For example, patients with small bowel NETs, even in disseminated disease, generally undergo resection of the primary tumour (or tumours because the may be multiple) and of mesenteric metastases to prevent future bowel obstruction and ischaemia. Patients with somatostatin receptor positive NETs generally receive monthly injection therapy with long acting somatostatin analogues to relieve hormonal symptoms but the treatment has also shown an antiproliferative effect [6]. Locoregional therapies include intra- or transarterial (chemo)embolisation of liver metastases (TACE) with gelfoam or 90Y-labelled microspheres.
Local ablative procedures comprise for example radiofrequency ablation (RFA) of liver metastases. Chemotherapy has no role in NET therapy except in highly proliferative pNETs and G3 tumours (poorly differentiated neuroendocrine carcinoma). New targeted therapies such as thyrosine kinase inhibitors, antiangiogenetic agents and mTOR inhibitors are currently evaluated in clinical trials. Somatostatin analogues may be labelled with beta-emitting radionuclides, for internal radiation of the tumours. Most commonly 177Lu labelled octreotate (177Lu-DOTATATE) and 90Y-labelled octreotide (90Y-DOTATOC) are infused intravenously for peptide receptor radiotherapy (PRRT) [7].
Section snippets
Computed tomography (CT)
Computed tomography (CT) is the basic imaging modality for the initial radiological work-up at presentation of the disease [8]. Similarly, CT is used for monitoring of NET therapy and in patients having undergone surgical resection, to detect recurrent disease. In modern CT scanners, a large number of detectors are arranged in parallel rows (multidetector CT, MDCT) and by use of a rapidly rotating X-ray tube, typically more than a hundred 1 mm sections are produced per second. Because the
Gastro-duodenal NETs
Endoscopy is usually sufficient in small Type I and II gastric tumours. In larger >1 cm gastric tumours and duodenal NETs, EUS is used to detect invasion and regional lymph node metastases. For invasive gastric NETs, all Type III tumours and duodenal NETs, staging is performed by CT/MRI and SRI. These NETs typically metastasise to regional lymph nodes and liver. In advanced disease also bone metastases can appear.
Small bowel NETs
The primary tumour, or tumours for they can be multiple, is usually small and
Image monitoring of NET therapy
After surgical resection of a NET with curative intent, surveillance of the patient is generally life-long because recurrences may be seen after many years. For monitoring NET therapy, CT or MRI every 3–6 months is generally appropriate in low-grade tumours and after the first year every six months. In patients with stable disease, examination can be performed yearly. SRI is recommended after one or two years and when results of radiology, biochemistry and the patient's clinical status are
Summary
The diverse features of NETs makes imaging of these tumours a challenge. At the same time, their cellular and molecular characteristics have allowed for development of specialised functional imaging by scintigraphy and PET that utilise their somatostatin receptor expression and uptake and decarboxylation of amine precursors. The recent development of the general morphologic methods, CT and MRI, makes examination faster with better use of intravenous contrast media for imaging in various
Conflict of interest
None.
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