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Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours

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Carcinoid tumours belong to the family of neuroendocrine tumours with a capacity to take up and concentrate amines and precursors as well as peptides, and can thereby be detected by nuclear medicine techniques. These rare tumours are difficult to diagnose at earlier stages because of small size and multiplicity. Computed tomography (CT) and magnetic resonance imaging (MRI) are mostly of benefit for detection of larger primary tumours (1–3 cm) and liver and lymph-node metastases. A majority of carcinoid tumours express somatostatin receptors, particularly receptor type 2, and thus somatostatin receptor scintigraphy (SRS) can be used for detection and staging of carcinoid tumours. The detection rate of carcinoid tumours has been reported to be somewhere between 80 and 100% in different studies. The scintigraphy gives a good staging of the disease and detection of unexpected tumour sites, which were not determined by conventional imaging. This method also indicates content of somatostatin receptors, which might indicate efficacy of treatment with octreotide or other somatostatin analogues. Another new non-invasive technique for detection of carcinoid tumours is positron emission tomography (PET). The biological substance for study can be labelled for radioactive imaging with radionuclears, such as 11C, 15O and 18F, with emission of positrons. More than 95% of patients studied displayed high tracer uptake from PET with 11C-5HTP (5-hydroxytryptophan), which is significantly higher compared to both computer tomography and somatostatin receptor scintigraphy. MIBG has been used for decades to visualize carcinoid tumours, because MIBG is concentrated in the endocrine cells. It was initially developed to detect phaeochromocytomas of the adrenal with reported high sensitivity (87%) and specificity as high as 99%. The method can be used when other methods fail to localize carcinoid tumours and particularly when treatment with 131I-MIBG is being considered.

Tumour-targeted treatment for malignant carcinoid tumour is still investigational, but has become of significant interest with the use of radiolabelled somatostatin analogues. Since a majority of carcinoid tumours present somatostatin receptors and can therefore be visualized in vivo by using radiolabelled somatostatin analogues, it seems logical to try to target these tumours with radioactive substances, not only for visualization but also for treatment.

111Indium-DTPA-octreotide has been used as the first tumour-targeted treatment, with rather low response rates (in the order of 10–20%) and no significant tumour shrinkage. The second radioactive analogue which has been applied in the clinic is 90yttrium-DOTA-Tyr3-octreotide, which has given partial and complete remissions in 20–30% of patients. The most significant side-effects have been kidney dysfunction, thrombocytopenia and liver toxicity. The most recent compound is 177lutetium-DOTA-Tyr3-octreotate, which has been applied by the Rotterdam group and has been reported to give partial remission in about 40% of the patients. In the near future, combined treatment with both 90yttrium and 177lutetium coupled to a somatostatin analogue might come into clinical trials. 177Lutetium may be more effective for smaller tumours whereas 90yttrium may be more effective for larger tumours.

Section snippets

Somatostatin receptor scintigraphy (SRS)

Somatostatin receptors are structurally related membrane glycoproteins. At the moment, five subtypes of human somatostatin receptors have been cloned.8, 9 The somatostatin analogue octreotide binds with high affinity to receptor subtypes 2 and 5. The expression of somatostatin receptors 2 and 5 is present in 70–90% of carcinoid tumours.10 Therefore, the radioactively labelled somatostatin analogue can allow visualization and staging of carcinoid tumours expressing somatostatin receptors 2 and 5.

Positron emission tomography (PET)

PET is a non-invasive technique for measurement of regional tracer accumulation and quantification. A biological substance for study can be labelled for radioactive imaging with radionuclides such as 11C, 15O and 18F with emission of positrons. The positrons generate photons, which are detected by a special camera. The half-lives of standard positron emitters are as follows: 18F, 110 minutes; 11C, 20 minutes; and 15O, 2 minutes.18 The use of PET in clinical oncology has significantly increased

123I- or 131I-meta-iodobenzylguanidine (MIBG)

MIBG has been used for many years to visualize carcinoid tumours as it is concentrated in endocrine cells.6 The method was initially developed to detect phaeochromocytomas of the adrenal with reported high sensitivity (87%) and specificity as high as 99%. The uptake of MIBG shares the same mechanism as norepinephrine. MIBG scintigraphy for carcinoid tumours has shown lower sensitivity than somatostatin receptor scintigraphy (50%).22 The method can be used when other methods have failed to

Tumour-targeted treatment

A new treatment modality for malignant carcinoid tumour is the use of radiolabelled somatostatin analogues. The majority of carcinoid tumours possess somatostatin receptors and can therefore be visualized in vivo by using radiolabelled somatostatin analogue 111indium-DTPA-octreotide (Octreoscan®). Therefore, it is logical to target these tumours with radioactive substances, not only for visualization but also for treatment.

Summary

Carcinoid tumours provide problems in diagnosing and localizing small tumours. Although computed tomography and magnetic resonance imaging techniques have significantly improved during the last year, small primary tumours in the gastrointestinal tract remain difficult to detect. Therefore, new techniques such as somatostatin receptor scintigraphy and PET-scanning have significantly improved the localization of carcinoid tumours. The staging of the disease is very important for selection of the

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