Evaluation of (111)In-pentetreotide, (131)I-MIBG and bone scintigraphy in the detection and clinical management of bone metastases in carcinoid disease

Bone metastases are assumed to be rare in carcinoid disease and to be associated mainly with bronchial primaries. The aim of the present study was to evaluate the occurrence of bone metastases in patients with metastatic carcinoid tumours, and the role of various nuclear medicine modalities (bone scintigraphy, (111)In-pentetreotide and (131)I-MIBG) in its detection and clinical management. Nine (2 women, 7 men, median age 65 years) out of 86 consecutive carcinoid patients treated between 1987 and 1998 developed bone metastases (10%) with a median interval of 37 months between the diagnosis of metastatic carcinoid and bone metastases. Seven of them had non-bronchial primaries. (111)In-pentetreotide scintigraphy failed to detect the bone lesions in 50% of the cases, and (131)I-meta-iodobenzylguanidine(MIBG) scintigraphy in almost 80% of cases. Standard bone scintigraphy, however, was positive in all. Pain relief of bone metastases by means of radiation therapy was obtained in 5 of 6 patients. In another patient palliation of pain symptoms was obtained with Rhenium-186-hydroxyethylidene diphosphonate. Octreotide, Interferon of MIBG were ineffective for this purpose. It is concluded that bone metastases in carcinoid patients may be missed on (131)I-MIBG and (111)In-pentetreotide scintigraphy. Bone scintigraphy is a sensitive imaging technique. Diagnostic nuclear medicine modalities may be helpful in the clinical management of carcinoid disease.     

Metaiodobenzylguanidine and somatostatin in oncology: role in the management of neural crest tumours

Two recently developed radiopharmaceuticals, iodine-131 metaiodobenzylguanidine (MIBG) and indium-111 pentetreotide, are currently being used for the diagnosis and therapy of neural crest tumours by interaction with the characteristic features of these tumours, such as an active uptake-I mechanism at the cell membrane and the presence of vesicles or neurosecretory granules in the cytoplasm and of specific receptors at the cell membrane. This review focusses on the role of MIBG and somatostatin analogues in the management of neural crest tumours. A number of aspects of both tracers are compared and the cumulative results are reviewed. Other uses of these radiopharmaceuticals are mentioned. It is concluded that both ¹¹¹In-pentetreotide and ¹²³I/¹³¹-MIBG are sensitive indicators of neural crest tumours, and have a complementary role. Unlike MIBG, ¹¹¹In-pentetreotide is not specific for neural crest tumours, as scintigraphy is also positive in many other tumours, granulomas and autoimmune diseases. ¹³¹I-MIBG is effective in the therapy of several neural crest tumours; the biodistribution of ¹¹¹In-pentetreotide at present does not allow radionuclide therapy using a beta-emitting label. However, as an indicator of somatostatin receptors, ¹¹¹In-pentetreotide scintigraphy may be a predictor of response to palliative treatment with unlabelled octreotide. Recommendations for the use of these procedures are given.This paper was presented at the European Association of Nuclear Medicine Congress 1993, in Lausanne (Switzerland).     

Functional imaging as an aid to decision-making in metastatic paraganglioma

Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.     

Patient dosimetry for 131I-MIBG therapy for neuroendocrine tumours based on 123I-MIBG scans

Pre-therapeutic metaiodobenzylguanidine (MIBG) scans can be performed using labelling with either iodine-123 or iodine-131. (123)I-MIBG scans provide better image quality and count statistics, while (131)I-MIBG allows registration of tracer kinetics over a longer period. The aim of this study was to determine how much information about the (131)I-MIBG therapy total body dose according to the MIRD formalism can be gathered from (123)I-MIBG pre-therapy scans. Thirty-eight (131)I-MIBG therapies administered to a total of 15 patients suffering from neuroblastoma ( n=6), carcinoid tumours ( n=5), phaeochromocytoma ( n=3) and medullary thyroid carcinoma ( n=1) were included. The mean administered activity was 5.3 GBq (SD 2.4 GBq). Three biplanar (123)I-MIBG total body scans were taken only once before a series of therapies while three biplanar (131)I-MIBG scans were taken after each therapy. Attenuation correction was performed taking into account the difference in attenuation between (123)I and (131)I. Using the MIRD formalism, the total body dose to the patient was calculated on the basis of: (1) a single exponential fit drawn through the data from the (123)I-MIBG pre-therapy scans, (2) a bi-exponential fit through the combined data of (123)I-MIBG pre-therapy and (131)I-MIBG post-therapy scans. The mean total body dose calculated in our study was significantly higher for patients suffering from neuroblastoma (mean+/-SD 0.37+/-0.21 mGy/MBq) than for patients suffering from phaeochromocytoma (0.08+/-0.02 mGy/MBq), carcinoid tumours (0.07+/-0.01 mGy/MBq) and medullary thyroid carcinoma (0.09 mGy/MBq). The correlation coefficient between the dose calculated on the basis of the (123)I-MIBG pre-therapy scans and the subsequent (131)I-MIBG therapy was 0.93 when a correction factor of 1.26 was taken into account. When considering all following therapies, the correlation was 0.85 and the correction factor, 1.20. Our results show that it is feasible to use data from pre-therapy (123)I-MIBG scans to calculate the total body dose of the subsequent (131)I-MIBG therapy.     

Comparison of somatostatin analogue and metaiodobenzylguanidine scintigraphy for the detection of carcinoid tumours

The purpose of this prospective study was to compare the ability of radiolabelled somatostatin analogue (RSA) and metaiodobenzylguanidine (MIBG) scintigraphy to display carcinoid tumours. Forty patients were studied after radiological assessment based on clinical symptomatology. These patients had radiologically demonstrated tumours (n=28), resected tumours discovered to be of the carcinoid type (n=5) or clinically and biologically suspected carcinoid tumours (n=7). They underwent indium-111 DTPA-pentetreotide or iodine-123-Tyr-3-octreotide and¹³¹I-MIBG scintigraphy. The results were compared with those of complementary surgical or morphological examinations and analysed according to the site of the tumour and the symptomatology. In the case of 31 patients with a total of 55 tumoral sites, the sensitivity of the initial radiological assessment, of RSA and of MIBG was 96%, 86% and 64%, respectively, for the detection of at least one tumour per patient, but 51%, 85% and 51%, respectively, for the total number of sites. No site was detected solely by MIBG. The concordance between RSA and MIBG was better when all sites were considered (kappa index+0.44) than for only extrahepatic abdominal tumoral sites (kappa index+0.095). Abdominal, thoracic or bone marrow tumours were more easily detected with RSA than with MIBG. Hepatic invasion (21 cases) was more easily detected by radiology (sensitivity 100%) than by RSA and MIBG, both of which displayed a sensitivity of 80%, but with differences in uptake intensity. Tumour detection using MIBG was more significantly linked with flush (P<0.01) than with diarrhoea (P>0.10). In the assessment of carcinoid tumours, RSA scintigraphy should be carried out initially (just after hepatic ultrasonography) and supplemented by MIBG, as comparison of the studies serves to guide therapeutic options and might be valuable for prognosis.     

Iodine-123 as a diagnostic imaging agent in differentiated thyroid carcinoma: a comparison with iodine-131 post-treatment scanning and serum thyroglobulin measurement

Purpose Using ¹²³I for diagnostic purposes avoids the risk of stunning for subsequent radioiodine treatment and affords an excellent image quality. In this study we assessed the role of ¹²³I in comparison with ¹³¹I post-treatment imaging in patients with thyroid cancer. Methods We compared a total of 292 ¹²³I scans with their corresponding post-treatment ¹³¹I images. Patients received a therapeutic dose of ¹³¹I following diagnostic scanning with 50–111 MBq of ¹²³I. All patients were in a hypothyroid state (>30 μIU/l) before radioiodine administration for either diagnostic or therapeutic purposes. Results In 228 out of 263 patients with a positive diagnostic scan, ¹²³I whole-body scan findings were concordant with those of corresponding post-treatment ¹³¹I images (concordance rate 87%). However, there were 44 additional foci of abnormal uptake on post-treatment ¹³¹I scans in 22 discordant cases with no impact on therapeutic management of the patients. In 13 patients, there was at least one new site on post-treatment images that had been missed on pretreatment ¹²³I images. Twenty-nine patients with a negative diagnostic scan were treated with ¹³¹I owing to a high serum thyroglobulin level (range 11.3–480 ng/ml). Radioiodine uptake sites were seen in eight post-treatment scans. In 21 pairs of whole-body scans, both the pre- and the post-treatment scan were negative (concordance rate 72.4%). Conclusion ¹²³I scanning is comparable to high-dose ¹³¹I post-treatment imaging in thyroid carcinoma patients, and ¹²³I offers excellent image quality as a diagnostic agent. It avoids disadvantages such as stunning before treatment and delivery of a high radiation dose to patients.     

Functional imaging of malignant paragangliomas and carcinoid tumours

Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared ¹²³I-MIBG, ¹¹¹In-[D-Phe¹]-DTPA-octreotide and ¹⁸F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of ¹¹¹In-[D-Phe¹]-DTPA-octreotide and ¹²³I-MIBG. Whole-body PET scans were performed 45 min after injection of ¹⁸F-FDG. ¹¹¹In-[D-Phe¹]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, ¹⁸F-FDG PET was positive in 11/15 patients and identified 107 lesions and ¹²³I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. ¹⁸F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease.     

Functional imaging of malignant paragangliomas and carcinoid tumours

Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared 123I-MIBG, 111In-[D-Phe1]-DTPA-octreotide and 18F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of 111In-[D-Phe1]-DTPA-octreotide and 123I-MIBG. Whole-body PET scans were performed 45 min after injection of 18F-FDG. 111In-[D-Phe1]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, 18F-FDG PET was positive in 11/15 patients and identified 107 lesions and 123I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. 18F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease.     

Enhancement of 131I-MIBG uptake in carcinoid tumours by administration of unlabelled MIBG

Iodine-131 metaiodobenzylguanidine (131I-MIBG) has been used with success for the palliation of symptomatic, metastatic carcinoid tumours. However, only 70% of cases are MIBG-avid and tumour uptake is not always sufficient for therapy. At The Netherlands Cancer Institute 34 carcinoid patients with no or insufficient uptake were treated with escalating doses of unlabelled ('cold') MIBG. No objective remissions were recorded, but a palliative effect (i.e. subjective disappearance of symptoms and/or reduction of medication by more than 50%) was observed in 60% of cases (mean duration 4.5 months). In 24 of the patients undergoing therapy with 'cold' MIBG, total body scintigraphy using 37 MBq 131I-MIBG was performed before and after infusion of 'cold' MIBG. The biodistribution of 131I-MIBG and its tumour to non-tumour ratios were compared. After 'cold' MIBG the 131I-MIBG uptake in the salivary glands was suppressed in all patients, myocardial uptake in 21, and uptake in normal liver tissue in 14. Pulmonary uptake was increased in 13 patients. More importantly, the tumour to non-tumour (T/NT) ratios improved in 17 of the 24 cases (by 7.8-111.4% at 24 h). Of the initial six patients demonstrating a significant increase in the T/NT ratio, five have subsequently received combined treatment of 7.4 GBq 131I-MIBG following the administration of 'cold' MIBG (both by 4 h intravenous infusion), resulting in a good palliative response in four of them. These patients had previously been excluded from therapy with 131I-MIBG only. It is concluded that the administration of unlabelled MIBG may not only provide palliation to patients with carcinoid tumours, but may also alter the biodistribution of MIBG, enabling 131I-MIBG therapy to be used in cases not qualifying for this treatment due to insufficient tumour uptake.     

Detection of metastatic medullary thyroid cancer with 131I-MIBG scans in Sipple's syndrome

While ¹³¹I-meta-iodobenzyl guanidine (¹³¹I-MIBG) scanning has made possible the scintigraphic visualization of pheochromocytoma and neuroblastoma, an accumulation of this agent has recently been reported in medullary thyroid cancer. We present the case of a patient with Sipple's syndrome (multiple endocrine neoplasia type IIa), in whom we were able to identify distant metastases and local invasion of medullary thyroid cancer as well as primary thyroid tumour and right adrenal pheochromocytoma, using ¹³¹I-MIBG scans. This case highlights the usefulness of ¹³¹I-MIBG in the detection of metastatic medullary thyroid cancer and suggests that this agent may also be of therapeutic use in the treatment of tumours.     

The role of I-131-MIBG in the diagnosis and therapy of carcinoids

The successful use of ¹³¹I-MIBG for the diagnosis and treatment of pheochromocytoma and neuroblastoma has led to its application in patients with carcinoid, another neural crest tumor. The present report describes the scintigraphic findings, in correlation with clinical and biochemical parameters, in 20 patients with histologically proven carcinoids. ¹³¹I-MIBG total body scintigraphy was positive in 12 and equivocal in 1 of 19 patients with metastases. The necessity of delayed imaging and the possible advantage of single photon emission tomography for the detection of this tumor are emphasized. The results of ¹³¹I-MIBG treatment in five patients with progressive carcinoid metastases are discussed. It is concluded that ¹³¹I-MIBG has a role in the work up of patients with proven carcinoid and can be used for palliative treatment of this tumor.     

[123I]Mtr-TOCA, a radioiodinated and carbohydrated analogue of octreotide: scintigraphic comparison with [111In]octreotide

Purpose Scintigraphy with maltotriose-[¹²³I]Tyr³-octreotate ([¹²³I]Mtr-TOCA) is compared with [¹¹¹In]DTPA-Phe¹-octreotide ([¹¹¹In]OC) to assess the differences in pharmacokinetics and imaging properties as well as to estimate the therapeutic potential of the corresponding [¹³¹I]Mtr-TOCA.Methods Six patients with somatostatin receptor (sstr)-positive tumours were assessed using a dual-head gamma camera. After injection of 137±28 MBq [¹²³I]Mtr-TOCA, dynamic data acquisition of the upper abdomen (30 min) was performed followed by whole-body scans at 0.5 h, 1 h, 3 h and 20 h as well as by SPECT imaging (tumour) at 2 h. [¹¹¹In]OC scintigraphy was performed by acquiring whole-body scans (4 h, 24 h) and SPECT (24 h). Using a region of interest (ROI) method, tissue and tumour bound activity was assessed and dosimetry performed.Results [¹²³I]Mtr-TOCA shows rapid tumour uptake. Up to 4 h, tumour/organ (tu/org) ratios are stable and generally higher than with [¹¹¹In]OC. From 3 h to 20 h, tu/org ratios increase for spleen, remain stable for liver and decrease significantly for all other tissues. In contrast, with [¹¹¹In]OC, tu/org ratios decrease slightly between 4 h and 24 h for liver, spleen and kidney and increase for all other tissues. On [¹²³I]Mtr-TOCA scintigraphy, a total of 27 lesions are detected, whereas 33 lesions are detected on [¹¹¹In]OC scintigraphy (p=0.50). Effective patient absorbed dose is 1.9±0.9 mSv per 100 MBq [¹²³I]Mtr-TOCA.Conclusion Compared with [¹¹¹In]OC, [¹²³I]Mtr-TOCA enables faster imaging of sstr-positive tumours with a lower radiation burden to the patient. [¹²³I]Mtr-TOCA and [¹¹¹In]OC allow for tumour imaging with almost identical contrast and diagnostic yield. As regards peptide receptor radionuclide therapy, radioiodinated Mtr-TOCA is hampered by limited intratumoural activity retention.     

Concentration of 123I-metaiodobenzylguanidine in left and right liver lobes. Findings indicate regional differences in function in the normal liver

PURPOSE: Normal radioactivity in the liver is often shown to be higher in the left lobe than in the right lobe at clinical examination by single photon emission computed tomography (SPECT) with 123I-metaiodobenzylguanidine (123I-MIBG). Our objective was to determine whether this represents a pathological condition. MATERIAL AND METHODS: The distribution of 123I-MIBG in the liver was retrospectively studied in clinical patients who had normal CT examinations of the liver and spleen. In the SPECT sections of 27 123I-MIBG examinations, we determined the activity ratios between the left and right lobes. The control group comprised 33 examinations with (111)In-pentetreotide (OctreoScan) and 23 examinations with 99mTc-antigranulocyte antibody. RESULTS: The mean activity ratio between left and right lobes for 123I-MIBG was 1.24, and for (111)In-pentetreotide 0.87. These figures differed significantly both from each other and from 1.00. The mean ratio for 99mTc-antibody at the early examinations was 0.99, and at the late examinations 0.95. These figures differed significantly from the values for 123I-MIBG and (111)In-pentetreotide. CONCLUSION: The increased concentration of 123I-MIBG in the left lobe of the liver compared to the right lobe is a normal finding. The reason for this cannot be explained. The difference in the way in which the left and right lobes deal with the three radiopharmaceuticals is a new finding and indicates a regional difference in liver function that has not been reported previously.     

111In-pentetreotide and123I-MIBG for detection and resection of lymph node metastases of a carcinoid not visualized by CT, MRI or FDG-PET

A patient with a history of a jejunal carcinoid and resection of liver metastases underwent CT, MRI and FDG-PET as well as somatostatin receptor scintigraphy using 111In-pentetreotide during follow-up. Octreoscan demonstrated one extrahepatic abdominal lesion with pathologic uptake, while the other imaging modalities failed to show a corresponding abnormality. For verification of this finding 123I-MIBG scintigraphy was performed. The MIBG scan confirmed the octreotide positive lesion and showed an additional abdominal lesion in the SPECT study. According to the scintigraphic results, radioguided surgery (RGS) was implemented using 123I-MIBG. This resulted in the intra-operative detection of two para- and pre-aortic lymph node metastases by the gamma probe and successful resection. An additional preaortal lymph node, suspicious by palpation, was also removed. Histopathology revealed metastases of a carcinoid tumor in all three specimens. In conclusion, the use of RGS facilitates successful removal of carcinoid metastatic lesions despite negative conventional imaging results. Secondly, 123I-MIBG scintigraphy may provide advantages over octreoscan for preoperative localization as well as radio-guided surgery of neuroendocrine metastatic lesions, if the involved site is located in proximity to highly octreotide-avid organs such as the kidneys or spleen.     

Noninvasive identification of left ventricular involvements in arrhythmogenic right ventricular dysplasia: Comparison of123I-MIBG,201TlCl, magnetic resonance imaging and ultrafast computed tomography

We examined the feasibility of myocardial¹²³I-MIBG,²⁰¹TlCl, magnetic resonance imaging (MRI) and ultrafast computed tomography (UFCT) for the early detection of left ventricular involvements in 15 patients with arrhythmogenic right ventricular dysplasia (ARVD). Radionuclide ventriculography (RNV) and myocardial imaging with¹²³I-MIBG,²⁰¹TlCl, MRI and UFCT were performed in all 15 patients and in 10 normal subjects. The patients’ scans were visually interpreted by two nuclear medicine physicians taking into consideration the extent score (ES) and severity score (SS) calculated by using the bull’s-eye view in relation to normal data derived from the normal subjects. The left ventricular ejection fraction (LVEF) was measured by RNV. Fourteen (93%) patients showed regional¹²³I-MIBG defects, while 12 (80%) patients showed regional²⁰¹TlCl defects. The ES and SS were higher in¹²³I-MIBG than²⁰¹TlCl (ES: 31.5± 18.5 vs. 17.5+18.2, p < 0.01, SS: 34.8±42.2 vs. 16.9±37.5, p< 0.01). Abnormal UFCT and MRI findings suggesting fatty involvements of the LV myocardium were demonstrated in 7 patients (Group B), while 7 patients showed regional¹²³I-MIBG defects without abnormal UFCT and MRI findings (Group A).¹²³I-MIBG was significantly more sensitive than UFCT and MRI (p< 0.05), although one patient, an exception, showed abnormal UFCT findings for the apex of the LV myocardium without abnormal¹²³I-MIBG and MRI findings. The LVEF, as a measure of LV systolic function, was better preserved in Group A than in Group B (59.3±3.6 vs. 45.8±5.8, p< 0.01). The present findings indicated that myocardial imaging with¹²³I-MIBG sensitively detects myocardial damage in patients with ARVD in the early stage when cardiac systolic function is still preserved.     

Scintigraphic detection of recurrence of medullary thyroid cancer

A case of recurrent medullary thyroid cancer (MTC) was evaluated with¹²³I-MIBG,^99mTc(V)-dimercaptosuccinic acid (DMSA), and²⁰¹Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a. recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although^99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to¹²³I-MIBG scintigraphy, it did not demonstrate the tumor site but²⁰¹Tl and¹²³I-MIBG did. Furthermore,¹²³I-MEBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both¹²³I-MIBG and^99mTc(V)-DMSA should be performed in the detection of recurrent MTC.     

High 123I-MIBG uptake in neuroblastic tumours indicates unfavourable histopathology

Purpose

Scintigraphy using ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) is widely used for the detection of neuroblastic tumours. The aim of this study was to identify a possible correlation between the uptake intensity on ¹²³I-MIBG SPECT and histopathology of neuroblastic tumours.

Methods

¹²³I-MIBG SPECT examinations were performed in 55 paediatric patients with neuroblastic tumour and compared to histopathology after surgical resection or biopsy at a mean of 2 weeks after SPECT. For each lesion International Neuroblastoma Pathology Classification System (INPC) stage, mitosis karyorrhexis index (MKI), location and a semiquantitative tumour-to-liver count-rate ratio (TLCRR) were determined. Also, the presence or absence of MYCN amplification, p1 deletion, urine catecholamine and neuron-specific enolase blood levels at the time of scanning were recorded.

Results

In the 55 patients, 61 lesions were evaluated with ¹²³I-MIBG SPECT and corresponding histopathological findings were reviewed (11 ganglioneuroma, 11 ganglioneuroblastoma and 39 neuroblastoma). TLCRR was significantly higher in the neuroblastoma group (mean TLCRR 2.7) than in the ganglioneuroblastoma group (mean TLCRR 1.0) and ganglioneuroma group (mean TLCRR 0.7) at the time of primary diagnosis (p?<?0.001) and at follow-up (p?=?0.039). Intense ¹²³I-MIBG uptake was found in tumour tissue with a high mitotic activity (MKI-high or MKI-intermediate) after treatment. Four ganglioneuromas (36 %), three ganglioneuroblastomas (27 %) and six neuroblastomas (15 %) were ¹²³I-MIBG-negative.

Conclusion

In paediatric patients with peripheral neuroblastic tumours, strong ¹²³I-MIBG uptake indicates unfavourable histopathology. High uptake was seen in neuroblastomas and in tumours with a high mitotic activity.     

99mTc-EDDA/HYNIC-octreotate scintigraphy, an efficient method for the detection and staging of carcinoid tumours: results of 3 years’ experience

Purpose At all stages of the disease, serious difficulties are encountered in the imaging diagnosis of carcinoids. Somatostatin receptor scintigraphy (SRS) holds great promise for detecting primary tumours and metastases. ^99mTc-EDDA/HYNIC-octreotate should significantly improve the diagnosis of carcinoids in comparison with ¹¹¹In-Octreoscan owing to the better affinity for SSR2 and the higher count rate. The aim of this study was to assess the diagnostic efficiency of ^99mTc-EDDA/HYNIC-octreotate scintigraphy in the detection and staging of carcinoid tumours.Methods The study population comprised 75 patients (age 48.5±15.5 years): 46 with histological confirmation of carcinoid and 29 with suspected disease. ^99mTc-EDDA/HYNIC-octreotate (740 MBq) SRS and CT were performed in all patients. Fifteen patients were examined with ¹¹¹In-Octreoscan. Results High-quality ^99mTc-EDDA/HYNIC-octreotate images were obtained in all cases, with maximum tumour tracer accumulation 4 h p.i. The mean target/non-target ratios for whole body (WB) and SPECT scans were, respectively, as follows: primary lesions: 4.5 and 10.2; metastases: liver, 3.1 and 12.3; abdominal focal lesions, 2.7 and 5.8; lung, 2.7 and 8.3; mediastinum, 3.4 and 7.6; bones, 6.8 and 19.0. ^99mTc-EDDA/HYNIC-octreotate WB scans revealed more metastases than ¹¹¹In-Octreoscan, with better individual separation. ^99mTc-EDDA/HYNIC-octreotate SRS revealed new metastatic lesions in seven patients with confirmed carcinoid, and in four with dissemination the primary focus was found. Five patients qualified for radioguided surgery and 11 were referred to ⁹⁰Y-DOTA-TATE therapy. The sensitivity of SRS in comparison with CT was higher for primary lesions and liver and abdominal lymph node metastases. In the subgroup of patients with suspected neuroendocrine tumours, two duodenal carcinoids, one thymic carcinoid and one ileal carcinoid were found.Conclusion ^99mTc-EDDA/HYNIC-octreotate, with high imaging quality, is an excellent alternative to ¹¹¹In-Octreoscan for staging of carcinoids, and it seems to be the method of choice for detection of the primary focus in patients with metastases from an unknown primary tumour.     

A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of 131I-MIBG (110 MBq) and with 131I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with 131I-chCE7, the subcutaneous tumours nearly disappeared; treatment with 131I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with 131I-mAb chCE7 and of 24 days with 131I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by 131I-chCE7 compared with 131I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with 131I-MIBG and 131I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. 131I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not accumulate 131I-MIBG, and the antibody may hold potential for radioimmunotherapy, either by itself or in combination with 131I-MIBG.     

Breast cancer staging using technetium-99m sestamibi and indium-111 pentetreotide single-photon emission tomography

We evaluated the clinical usefulness of single-photon emission tomography (SPET) with technetium-99m sestamibi and indium-111 pentetreotide in breast cancer staging. Fifteen patients with clinical and/or mammographic findings suggesting T1-2N0-1 breast cancer were studied. SPET images were acquired 20 min after^99mTc-sestamibi injection and 4 and 24 h after¹¹¹In-pentetreotide injection. Patients underwent surgery the day after the later¹¹¹In-pentetreotide acquisition. Pathological examination showed 16 tumours in the 15 patients, with one bilateral carcinoma. The mean tumour diameter was 18.7 mm. Metastatic axillary involvement was found in 6/16 tumours, with a mean of five metastatic nodes per axilla. Both tracers correctly identified 15/16 primary tumours and five of the six cases of metastatic axillary node involvement. No difference between the tracers was observed in breast cancer staging.^99mTc-sestamibi seems to be the better tracer in terms of physical characteristics, execution time and cost-effectiveness. Our data suggest the future possibility of using nuclear medicine imaging to avoid axillary dissection in patients with T1 breast cancer.