Comparison of somatostatin receptor imaging, computed tomography ...

Original article Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours Arturo Chiti1, Stefano Fanti2, Giordano Savelli1, Annadina Romeo2, Bartolomeo Bellanova2, Marcello Rodari1, Barbara J. van Graafeiland3, Nino Monetti2, Emilio Bombardieri1 1

Istituto Nazionale per lo Studio e la Cura dei Tumori, Division of Nuclear Medicine, Milan, Italy Policlinico S. Orsola Malpighi, Department of Nuclear Medicine, Bologna, Italy 3 Leiden University Medical Center, Department of Radiology, Division of Nuclear Medicine, Leiden, The Netherlands 2

&misc:Received 1 May and in revised form 29 June 1998

&p.1:Abstract. Neuroendocrine tumours displaying somatostatin receptors have been successfully visualised with somatostatin receptor imaging (SRI). However, there may be differences in sensitivity depending on the site of the primary tumour and/or its metastases. We studied 131 patients affected by neuroendocrine tumours of the gastro-entero-pancreatic (GEP) tract. A pathological diagnosis was obtained in 116 patients, while in 15 the diagnosis was based on instrumental results and follow-up. Fifty-one patients were examined for staging purposes, 80 were in follow-up. Images were acquired 24 and 48 h after the injection of 150–220 MBq of indium-111 pentetreotide. Whole-body and SPET images were obtained in all patients. Patients were also studied with computed tomography (CT), ultrasound (US), and other procedures. Tumours were classified according to their site of origin: pancreas n = 39, ileum n = 32, stomach n = 16, appendix n = 9, duodenum n = 5, jejunum n = 5, rectum n = 3, biliary tract n = 2, colon n = 2, caecum n = 1, liver metastases from unknown primary = 15, widespread metastases from unknown primary = 2. Sensitivity for primary tumour localisation was as follows: SRI = 62%; CT = 43%; US = 36%; other procedures = 45%. Sensitivity for liver metastases: SRI = 90%; CT = 78%; US = 88%; other procedures = 71%. Sensitivity for the detection of extrahepatic soft tissue lesions was: SRI = 90%; CT = 66%; US = 47%; other procedures = 61%. Sensitivity for the detection of the primary tumour in patients with metastases from unknown primary sites: SRI 4/17; CT 0/13; US 0/12; other procedures 1/10. In 28% of the patients SRI revealed previously unknown lesions, and in 21% it determined a modification of the scheduled therapy. Our study confirms the important role of SRI in the management of GEP tumours. Correspondence to: E. Bombardieri, Divisione Medicina Nucleare, Istituto Nazionale Tumori, Via Venezian, I-20133, Milano, Italy&/fn-block:

However, we feel that a critical investigation should address its role in locating primary tumours, in particular in patients with metastases from unknown primary sites. &kwd:Key words: Somatostatin receptors – Radionuclide imaging – Neuroendocrine tumours – Gastro-entero-pancreatic tract Eur J Nucl Med (1998) 25:1396–1403

Introduction The term neuroendocrine tumours is used to define a group of neoplasms by their secretory products and by certain cytoplasmatic proteins. When these rare tumours reproduce the functional characteristics of the parent cells, they cause specific syndromes. About 70% of these neoplasms originate from the pancreas, stomach, duodenum, jejunum, appendix, colon and rectum, and are called gastro-entero-pancreatic (GEP) tumours [1]. Neuroendocrine tumours of the GEP tract represent about 2% of all malignant gastrointestinal neoplasms [2]. Because of their heterogeneity in terms of histological differentiation, hormone production, and biological and clinical behaviour, a classification has been proposed based on the site of origin and biological behaviour of the tumour [3,4]. Neuroendocrine tumours of the pancreas, stomach, duodenum, jejunum and ileum, and colon and rectum are included in this classification. Neoplasms originating from the same site are subdivided into tumours with benign behaviour, low-grade malignancies, and highly malignant neoplasms. This classification is greatly facilitated by the new immunocytochemical and immunohistochemical methods employed for the pathological diagnosis of these neoplasms. European Journal of Nuclear Medicine Vol. 25, No. 10, October 1998 – © Springer-Verlag 1998

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A diagnosis is quite easy to make in biologically active tumours, which produce and release a variety of hormones and peptides. Patients often present with a clinical syndrome which entails a characteristic clinical picture. In these cases specific serum markers are very likely to lead to a correct diagnosis. After the clinical diagnosis, staging is required to locate the primary tumour and/or the metastatic spread. Diagnostic imaging is pivotal in this phase. Computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), echoendoscopy, selective arteriography and nuclear medicine techniques are the diagnostic tools available to the clinician in the staging procedure. In some cases, when diagnostic imaging is ineffective, a surgical look may be necessary, often associated with intraoperative US. Diagnosis is often late in the case of biologically inactive tumours. Symptoms derive from the growing tumour and, as these tumours are usually slow-growing, years may go by without the patient being aware of his/her disease. Often the first sign is a coincidentally discovered tumour of the appendix during an appendectomy, or several liver metastases without evidence of a primary tumour [5]. In the diagnostic approach to neuroendocrine tumours, nuclear medicine procedures are currently gaining interest [5]. This is due to the introduction of new tracers and to the technological improvement of radiation detection instruments. The most widely used radiopharmaceutical at present is a somatostatin analogue, octreotide, radiolabelled with indium-111. This peptide can be chelated with diethylene triamine penta-acetic acid (DTPA) and labelled with 111In to obtain 111In-pentetreotide (the term “pentetreotide” denotes DTPA-octreotide). This radiopharmaceutical is used to image somatostatin receptors type 2 and 5, which are usually expressed on neuroendocrine GEP tumours. Somatostatin receptor imaging (SRI) has been successfully employed to visualise somatostatin receptor-bearing tumours [6, 7]. The aim of our study was to assess the clinical value of SRI in the localisation of primary and metastatic neuroendocrine tumours of the GEP tract. Materials and methods One hundred and thirty-one patients with known or suspected neuroendocrine GEP tumours were enrolled in this study. The median age was 54 years, with a range from 16 to 83. There were 61 female and 70 male patients. A pathological diagnosis was obtained in 116 patients, while in 15 the diagnosis was based on instrumental results and follow-up. Fifty-one patients underwent SRI for staging purposes, while 80 were studied during follow-up. Using the above-mentioned classification, we classified the tumours according to their site of origin, as detailed in Table 1. Before undergoing SRI, 106 of the 131 patients underwent therapeutic procedures. In most cases they were treated with surgery, alone or in combination with medical therapies (Table 2). Eighteen patients were on palliative therapy with somatostatin analogues when they underwent SRI. The administration of somatostatin analogues was discontinued, at least 14 days before SRI when patients where on long acting pharmaceuticals and at

European Journal of Nuclear Medicine Vol. 25, No. 10, October 1998

Table 1. Classification of the tumours in 131 patients based on the site of the primary lesion&/tbl.c: &tbl.: Tumour site

No. of patients

Pancreas Ileum Stomach Liver metastases from unknown primary Appendix Duodenum Jejunum Rectum Biliary tract Colon Widespread metastases from unknown primary Caecum

39 32 16 15 9 5 5 3 2 2 2 1

&/tbl.: Table 2. Therapies performed before SRI&/tbl.c: &tbl.: Therapy

No. of patients

Surgery Surgery and chemotherapy Chemotherapy Surgery and somatostatin analogues Somatostatin analogues Surgery, chemotherapy and somatostatin analogues Chemotherapy and somatostatin analogues Surgery, chemotherapy and radiotherapy Radiotherapy and somatostatin analogues No treatment

60 17 10 9 4 2 2 1 1 25

&/tbl.: least 3 days before SRI when they were on the non-long-acting drug. In two patients complaining of severe symptoms due to the tumour secretions, the administration of the analogues (long acting formulation) was not discontinued. Both these patients were in follow-up, and all the known lesions were visualised with SRI. Thirteen patients underwent SRI without any evidence of neoplastic disease. Ten of these patients were studied to complete their staging after surgery, while three underwent SRI as a part of their follow-up. We also classified the tumours using the more commonly used classification based primarily on the histological subtype. Clustering tumours in this way, we studied 87 carcinoids, 11 gastrinomas, 3 insulinomas, 2 somatostatinomas and 2 glucagonomas. Twentysix patients had non-secreting tumours which were classified only as neuroendocrine GEP tumours. Details on classification of the tumours in this way are shown in Table 3. Whole-body and single-photon emission tomography (SPET) images were acquired 24 and 48 h after i.v. injection of 150–220 MBq of 111In-pentetreotide. When required, 72-h static images were obtained to check for radioactivity in the gut that could mimic pathological uptake. According to our previous experience, the optimal imaging technique was to acquire whole-body images 24 and 48 h after tracer administration, using a double-head gamma camera 256×1024 matrix, 50 mm/min, in anterior and posterior views. SPET studies were also performed 24 and 48 h after administration of the tracer using a triple-head gamma camera, 128×128,

1398 Table 3. sification of the tumours of the 131 patients based on the histological subtype and secretion pattern&/tbl.c: &tbl.: Tumour type

Site

Carcinoid

Ileum 29 Pancreas 14 Appendix 9 Liver metastases from 9 unknown primary Stomach 13 Duodenum 2 Jejunum 3 Rectum 3 Colon 2 Widespread metastases from 2 unknown primary Caecum 1

Non-secreting

Pancreas Liver metastases from unknown primary Stomach Duodenum-ileum Biliary tract

No. of patients

12 5 3 4 2

Gastrinoma

Pancreas Duodenum-jejunum

8 3

Insulinoma

Pancreas

3

Somatostatinoma

Duodenum Liver metastases from unknown primary

1 1

Glucagonoma

Pancreas

2

&/tbl.: zoom 1, 120 frames, 50 s/frame. Gamma cameras were equipped with medium-energy collimators, with a 20% energy window on both 111In energy peaks (171 and 245 keV). Transaxial SPET data were reconstructed and then filtered with a 3D low-pass filter (Butterworth order 8, cut-off 20–26). The patients were put on a low-fibre diet for 3 days before the administration of the radiopharmaceutical; polyethylene glycol (PEG) laxative was given afterwards to reduce the abdominal raTable 4. Results of SRI, CT, US and other methods in the detection of primary and metastatic lesions from neuroendocrine GEP tumours in 131 patients&/tbl.c: &tbl.:

dioactivity when the first set of images was acquired. If there were contraindications to PEG, senna derivatives were used. CT, US and other diagnostic procedures (plain X-ray, MRI, echoendoscopy, selective arteriography, bone scan) were performed according to the protocol issued by the GEP study group of the Italian Association of Nuclear Medicine (AIMN). All diagnostic procedures other than SRI were reported as interpreted by the referring physicians in the clinical record. In dubious cases the images of all diagnostic modalities were reviewed together. SRI images were interpreted by two experienced nuclear medicine physicians, who had knowledge of all clinical data on the patients.

Results Primary tumours were correctly identified with SRI in 34 of 55 patients, giving a sensitivity of 62%. In patients with liver metastases (Figs. 1–3), SRI and US had a comparable sensitivity (90% vs 88%), while CT scan showed a lower figure (78%). Excluding the primary tumour and liver lesions, soft tissue sites were detected by all diagnostic methods: abdominal lymph nodes (25 sites), pancreas (relapses in five sites), lung (three sites), ileum (five sites), spleen (four sites), mediastinal lymph nodes (two sites), cervical lymph nodes (one site) and brain (one site). Considering these lesions on a patient basis, we had 20 patients with abdominal lymph nodes, four with pancreatic relapses, four with ileal lesions, three with spleen lesions, one with a lung lesion, one with abdominal and mediastinal lymph nodes, one with abdominal lymph nodes and a pancreatic relapse, one with abdominal and cervical lymph nodes and a brain metastasis, one with an ileal relapse and a lung metastasis, one with a lesion in the right lung and a spleen lesion and one with mediastinal lymph nodes. In this setting SRI showed a sensitivity of 90%, missing abdominal lymph nodes in five patients and one pancreatic relapse. The sensitivity of CT, US and other methods was lower. Table 4 details the results expressed as sensitivity, specificity, accuracy, positive predictive value and negative predictive value. SRI

CT

US

Other

34/55 (62)

21/49 (43)

16/44 (36)

13/29 (45)

Liver metastases Sensitivity (%) Specificity (%) Accuracy (%) Pos. predictive value (%) Neg. predictive value (%)

66/73 (90) 56/58 (97) 122/129 (93) 66/68 (97) 56/63 (89)

53/68 (78) 38/43 (93) 91/109 (83) 53/56 (95) 38/53 (72)

52/59 (88) 41/43 (95) 93/102 (91) 52/54 (96) 41/48 (85)

20/28 (71) 14/14 (100) 34/42 (81) 20/20 (100) 14/22 (64)

Other soft tissue lesions Sensitivity (%) Specificity (%) Accuracy (%) Pos. predictive value (%) Neg. predictive value (%)

38/42 (90) 87/89 (98) 126/132 (95) 38/40 (95) 87/91 (96)

23/35 (66) 39/40 (98) 62/75 (83) 23/24 (96) 39/51 (76)

15/32 (47) 20/20 (100) 35/52 (67) 15/15 (100) 20/37 (54)

11/18 (61) 29/30 (97) 40/48 (83) 11/12 (92) 29/36 (81)

Primary tumour Sensitivity (%)

&/tbl.: European Journal of Nuclear Medicine Vol. 25, No. 10, October 1998

1399 Table 5. Previously unknown lesions first detected by SRI and subsequently confirmed in 37 patients&/tbl.c: &tbl.: Site of the lesions

No. of patients

Abdominal lymph nodes Pancreas (primary) Pancreas (relapse) Liver Skeleton Lung Ileum (primary) Ileum (relapse) Stomach (primary) Colon (primary) Brain

11 5 3 5 3 2 2 2 2 1 1

&/tbl.:

Bone lesions were demonstrated in 38 patients but SRI was positive in only nine of them. Bone scan was only performed in symptomatic patients with skeletal pain or as a staging procedure in patients who were candidates for liver transplantation because of massive metastatic involvement of the liver. Therefore, we did not study a sufficient number of patients with positive lesions to provide consistent data. SRI was the first diagnostic method able to detect previously unknown lesions which were confirmed afterwards in 37 of the 131 patients (28%). Details on the previously unknown lesions are shown in Table 5. Moreover, in 28 patients (21%) the therapeutic schedule was modified after SRI. This means that some surgical procedures were excluded after SRI or that a palliative treatment with somatostatin analogues was started following the demonstration of somatostatin receptors. When only patients with metastases from unknown primary sites were considered, the sensitivity of all diagnostic methods in revealing the primary tumour was very poor. In fact, SRI correctly located tumour sites in 4 out of 17 patients, CT in none out of 13 patients, and US in none out of 12 patients. Ten patients were also studied with other methods, but only one tumour was successfully detected using MRI. Calculating sensitivity for primary tumours after grouping the patients according to the classification based primarily on histological subtype, we found a sensitivity of 54% for SRI in 87 carcinoids and of 79% in 26 non-secreting neuroendocrine GEP tumours. Sensitivity and specificity of SRI for liver metastases and other soft tissue lesions were high in both carcinoids and non-secreting tumours. The results obtained classifying tumours into carcinoids and non-secreting tumours are shown in tables 6 and 7. The three primary gastrinomas we studied were detected by SRI, while US localised only one of the three tumours and CT was not able to localise any of these tumours. Three patients had liver metastases correctly visualised with SRI, CT and US, and there were no false-


a

b Fig. 1. a Whole-body scan acquired 24 h after the injection of 185 MBq of 111In-pentetreotide. A single metastasis can be seen in the right liver lobe. This patient was operated on for a neuroendocrine tumour of the colon. b Same case as in a. SPET study acquired soon after the whole-body scan, transaxial slice. The liver lesion is clearly defined in the right liver lobe&ig.c:/f

positive results in the eight patients without liver involvement. In gastrinoma patients, SRI also detected three out of five other soft tissue lesions, while US detected only one of these metastatic sites and CT none. Of the three patients affected by insulinomas, two had already undergone surgery. One of them had liver metas-

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a

Fig. 2. Non-consecutive transaxial slices of a SPET study acquired 24 h after the injection of 185 MBq of 111In-pentetreotide. The patient had a neuroendocrine tumour of the pancreas (P), a spinal metastasis (B) and multiple liver lesions (L)&ig.c:/f

b Fig. 3. a Abdominal CT scan of a patient with liver metastases from a neuroendocrine tumour of the ileum. b SPET study of the same patient as in a; transaxial slice. Images were acquired 48 h after the injection of 200 MBq of 111In-pentetreotide. Multiple liver lesions are sharply defined in the liver&ig.c:/f

tases that were negative on SRI but positive on CT and US. The only primary insulinoma in our series was correctly visualised in the pancreas with SRI, CT and US. One somatostatinoma was missed by all diagnostic procedures, but the patient had liver and bone metastases which were correctly visualised by SRI. The other patient had undergone surgery and had no evidence of metastatic involvement. The primary glucagonoma studied by us was positive on SRI, CT and US. The other had been surgically removed and liver metastases were detected by SRI, CT and US. Table 6. Sensitivity and specificity of SRI, CT, US and other methods in 87 carcinoid tumours&/tbl.c: &tbl.:

Discussion The published papers on SRI are characterised by inhomogeneous series of patients with respect both to stage and type of neoplasm. Also, some older papers reported on patients studied with [123I]-Tyr3-octreotide. Nonetheless, successful results have been described in the detection of neuroendocrine GEP tumours using SRI. SRI

CT

US

Other


19/35 (54)

15/30 (50)

10/27 (37)

9/20 (45)

Liver metastases Sensitivity (%) Specificity (%)

45/49 (92) 36/38 (95)

32/44 (73) 25/27 (93)

32/39 (82) 24/26 (92)

13/18 (72) 9/9 (100)

Other soft tissue lesions Sensitivity (%) Specificity (%)

23/27 (85) 56/60 (93)

16/20 (80) 28/28 (100)

9/21 (43) 11/11 (100)

7/10 (70) 23/23 (100)

&/tbl.: European Journal of Nuclear Medicine Vol. 25, No. 10, October 1998

1401 Table 7. Sensitivity and specificity of SRI, CT, US and other methods in 26 non-secreting neuroendocrine GEP tumours&/tbl.c: &tbl.:

SRI

CT

US

Other


11/14 (79)

6/14 (43)

4/12 (33)

3/7 (43)

Liver metastases Sensitivity (%) Specificity (%)

16/18 (89) 8/8 (100)

15/18 (83) 3/4 (75)

14/14 (100) 14/14 (100)

3/6 (50) 3/3 (100)

Other soft tissue lesions Sensitivity (%) Specificity (%)

8/9 (89) 17/17 (100)

7/9 (78) 7/7 (100)

5/5 (100) 5/5 (100)

2/4 (50) 6/7 (86)

&/tbl.:

Joseph et al. [8] studied 85 patients affected by GEP tumours and obtained a sensitivity of 89% with SRI. In 52% of the patients they concluded that SRI had the same clinical value as US and CT. SRI was considered superior in 34% and inferior in 14%. The Rotterdam group published an important study [9] in which they reported on 52 patients with carcinoid tumours. Using both 123I-Tyr3-octreotide and 111In-pentetreotide they correctly localised the primary tumour in 86% of the patients. Both these studies reported a low sensitivity for metastatic liver lesions, but they used only planar imaging, which has been demonstrated to have a lower sensitivity. Westlin et al. [10], Hammond et al. [11] and Modlin et al. [12] reported similar satisfactory results in limited series of patients. Schillaci et al. [13] reported on 18 patients with abdominal carcinoids. They compared SPET with planar imaging, CT and MRI and concluded that SRI SPET is essential for the correct evaluation of these patients. The group from Brussels [14] studied 47 patients affected by GEP tumours, reporting a high overall sensitivity for lesion detection (87%). Their results confirmed data from other authors, who reported sensitivities between 82% and 92% [10, 11, 15, 16]. This study [14] also reported a higher sensitivity for SRI (97%) when compared with traditional diagnostic imaging (70%). They underlined the advantages of the whole-body technique, which is cost-effective and well tolerated by patients. They also stressed the importance of SRI in selecting patients for somatostatin analogue therapy. Lebtahi et al. [17] compared SRI with conventional imaging in 160 patients affected by neuroendocrine GEP tumours. The overall sensitivity was 78%. SRI was positive in 61% of 46 patients having tumours previously undetected with conventional imaging and was negative in only 15% of the known tumour sites. SRI provided additional detection sites compared with conventional imaging, even if the detection rates were comparable (78% vs 71%). The classification of tumours was modified in 24% of the patients and the surgical approach was changed in 25%. The authors proposed SRI as a firstline procedure in patients with GEP tumours, selecting eligible patients for curative surgery from those with extrahepatic metastases. They also underlined that the ac-


curacy of SRI depends on the acquisition of multiple views and SPET. Kälkner et al. [18] studied 100 patients with carcinoid tumours and demonstrated a positive correlation between the finding of one or more lesions with SRI, urinary 5-hydroxyindoleacetic acid (U-5HIAA) and levels of chromogranin-A. They stated that the presence of somatostatin receptors and high levels of U-5HIAA can be considered a prognostic factor, suggesting the presence of a differentiated tumour. They reported a higher tumour/background ratio in patients treated with interferon or somatostatin analogues. This phenomenon has already been reported [19, 20], and should be one of the topics of discussion for future studies. Although many data are already available on the use of SRI, providing a basis on which to assess its value in clinical practice, our experience is focussed on selected patients affected by neuroendocrine tumours originating from the GEP tract. Studying a highly selected population of patients may better define the correct indications for SRI in these rare tumours. In particular, SRI is an expensive and time-consuming diagnostic approach, so it should be used only in patients who may really benefit from it. The pathological classification we followed in this study allows better definition of tumours, not only regarding their site of origin and biological behaviour, but also with respect to the therapeutic approach. In fact, we excluded neuroendocrine tumours originating from the lungs, such as bronchial carcinoids, which require a totally different surgical approach from GEP tumours. In our study, the overall sensitivity for primary tumour detection could not be considered satisfactory for all diagnostic modalities employed. However, SRI showed the highest sensitivity, leading us to consider this technique the procedure of choice in patient evaluation before surgery. Its value was more limited in patients with metastases from unknown primary sites. This is a small group of patients, but finding the primary tumour in such patients has a dramatic impact on patient management. However, it should be noted that all other diagnostic modalities had a near-zero sensitivity, leaving surgery as the only way to solve the diagnostic dilemma. This is a difficult problem. Probably the resolution needed to visualise the weak signal from such small tumours

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is well beyond the possibility of modern gamma cameras. Positron emission tomography using specifically designed radiopharmaceuticals will probably be the best way to image these neoplasms. The value of SRI in patient management is higher in the case of metastatic tumours. The sensitivity of SRI was superior to that of the other methods in detecting liver metastases, with a similar specificity. Also with respect to other sites of metastatic involvement, SRI had a higher sensitivity and similar specificity compared with the other diagnostic modalities. Abdominal metastatic lymph nodes require particular attention when using SRI, as it missed metastases in abdominal lymph nodes in 5 of 25 lesions, while CT scan missed only 1 of 21. A possible explanation may be that, although SPET improved the sensitivity in abdominal imaging, interference from kidneys, spleen and non-specific activity in the bowel reduced the chances of detecting abdominal lymph nodes. Therefore, when metastatic abdominal lymph nodes are to be excluded it is necessary to perform both CT scan and SRI. Another matter of debate is the value of SRI in patients with bone lesions. Our study shows that when there is a strong suspicion of metastatic bone involvement, SRI is not the procedure of choice. The clinician should consider plain X-ray and bone scan to visualise these metastases. Nonetheless, we had two patients in whom SRI was the first method to demonstrate bone involvement. These were important patients, as one was in follow-up after liver transplantation and the other underwent SRI as a staging procedure before liver transplantation. We also considered the more commonly used classification which subgroups the tumours primarily on the basis of histological subtype, in order that our data would be easily comparable with previous reports. We calculated the sensitivity and the specificity only for carcinoids and non-secreting tumours, as the other tumour groups included a limited number of patients. For gastrinomas, insulinomas, glucagonomas and somatostatinomas we only reported the detection rate of primary and metastatic lesions. Our results show that the sensitivity of SRI in detecting distant metastases was not different between carcinoids and non-secreting tumours. By contrast, comparing primary tumour detection in the two groups, we found a lower sensitivity (54%) in carcinoids than in non-secreting tumours (79%). Although we do not have a clear explanation for this difference, the result could have been affected by the difference in the number of patients studied in the two groups (87 vs 26), as sensitivity in the carcinoid group was lower than that in the non-secreting tumour group for all the diagnostic modalities. The overall sensitivity of SRI in detecting primary tumours and liver and soft tissue metastases in our study was 81%, which is in agreement with previous studies. This figure dropped dramatically to 71% when skeletal lesions were included. This confirms that SRI is in

general unsuitable for the detection of detect bone lesions from neuroendocrine GEP tumours. Our study lead us to affirm that, when carefully acquired and interpreted, SRI is able to provide important information in the diagnostic work-up of patients with neuroendocrine GEP tumours. The procedure may take full advantage of the whole-body technique and SPET, provided both acquisitions have high-count statistics. With whole-body imaging distant metastases may be detected with a single radiopharmaceutical injection. Doubtful lesions on whole-body scans can often be well defined with high-quality SPET, giving a high overall diagnostic accuracy. Our experience leads us to conclude that SRI is an essential imaging procedure in selected patients affected by neuroendocrine GEP tumours. References 1. Oberg K. Neuroendocrine gastrointestinal tumours. Ann Oncol 1996; 7: 453–463. 2. Solcia E, Capella C, Buffa R. Cytology of tumours in the gastroenteropancreatic and diffuse neuroendocrine system. In: Falkmer S, Akanson S, Sundler F, eds. Cytology of tumours of the neuroendocrine system. Amsterdam: Elsevier; 1984: 453–480. 3. Solcia E, Rindi G, Sessa F, Fiocca R, Luinetti O, Bosi F. Endocrine tumours of the gastrointestinal tract. In: Polak JM, ed. Diagnostic histopathology of neuroendocrine tumours. Edinburgh: Churchill Livingstone; 1993: 123–149. 4. Williams ED, Sandler M. The classification of carcinoid tumours. Lancet 1963; I: 238–239. 5. Seregni E, Chiti A, Bombardieri E. Radionuclide imaging of neuroendocrine tumors: biological basis and diagnostic results. Eur J Nucl Med 1998; 25: 639–658. 6. Lamberts SWJ, Reubi JC, Krenning EP. Somatostatin and the concept of peptide receptor scintigraphy in oncology. Semin Oncol 1994; 21(Suppl 13): 1–5. 7. Krenning EP, Kwekkeboom DJ, de Jong M, Visser TJ, Reubi JC, Bakker WH, Kooij PP, Lamberts SW. Essentials of peptide receptor scintigraphy with emphasis on the somatostatin analog octreotide. Semin Oncol 1994; 21(Suppl 13): 6–14. 8. Joseph K, Stapp J, Reinecke J, Skamel HJ, Hoffken H, Neuhaus C, Lenze H, Trautmann ME, Arnold R. Receptor scintigraphy with 111In-pentetreotide for endocrine gastroenteropancreatic tumors. Horm Metab Res 1993; 27(Suppl): 28–35. 9. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123ITyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993; 20: 716–731. 10. Westlin JE, Janson ET, Arnberg H, Ahlstrom H, Oberg K, Nilsson S. Somatostatin receptor scintigraphy of carcinoid tumours using the [111In-DTPA-D-Phe1]-octreotide. Acta Oncol 1998; 32: 783–788. 11. Hammond PJ, Arka A, Peters AM, Bloom SR, Gilbey SG. Localization of metastatic gastro-entero-pancreatic tumours by somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]octreotide. Q J Med 1994; 87: 83–87. 12. Modlin IM, Cornelius E, Lawton GP. Use of an isotopic somatostatin receptor probe to image gut endocrine tumors. Arch Surg 1995; 130: 367–374.


1403 13. Schillaci O, Scopinaro F, Angeletti S, Tavolaro R, Danieli R, Annibale B, Gualdi G, Delle Fave G. SPECT improves accuracy of somatostatin receptor scintigraphy in abdominal carcinoid tumors. J Nucl Med 1996; 37: 1452–1456. 14. Jamar F, Fiasse R, Leners N, Pauwels S. Somatostatin receptor imaging with indium-111-pentetreotide in gastroenteropancreatic neuroendocrine tumors: safety, efficacy and impact on patient management. J Nucl Med 1995; 36: 542–549. 15. Kwekkeboom DJ, Krenning EP, Bakker WH, Oei HY, Kooij PP, Lamberts SW. Somatostatin analogue scintigraphy in carcinoid tumours. Eur J Nucl Med 1993; 20: 283–292. 16. Lamberts SWJ, Reubi JC, Krenning EP. Somatostatin and the concept of peptide receptor scintigraphy in oncology. Semin Oncol 1994; 21(Suppl 13): 1–5. 17. Lebtahi R, Cadiot G, Sarda L, Daou D, Faraggi M, Petegnief Y, Mignon N, Le Guludec D. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neu-

roendocrine gastroenteropancreatic tumors. J Nucl Med 1997; 38: 853–858. 18. Kälkner KM, Janson ET, Nilsson S, Carlsson S, Oberg K, Westlin JE. Somatostatin receptor scintigraphy in patients with carcinoid tumors: comparison between radioligand uptake and tumor markers. Cancer Res 1995; 55(Suppl): 5801s–5804s. 19. Soresi E, Bombardieri E, Chiti A, Boffi R, Invernizzi G, Crippa F, Maffioli L. Indium-111-DTPA-octreotide scintigraphy modulation by treatment with unlabelled somatostatin analogue in small-cell lung cancer. Tumori 1995; 81: 125–127. 20. Dörr U, Räth U, Sautter-Bihl ML, Guzman G, Bach D, Adrian HJ, Bihl H. Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue. Eur J Nucl Med 1993; 20: 431–433.
