(dtpa-phe(1))-octreotide and Carcinoid-Tumor

This paper is a critical review of the literature on NET radionuclide therapy with (111)In-DTPA(0)-octreotide (Octreoscan) and (131)I-MIBG, focusing on efficacy and toxicity. Some potential future applications and new candidate therapeutic agents are also mentioned. Octreoscan has been a pioneering agent for somatostatin receptor radionuclide therapy. It has achieved symptomatic responses and disease stabilization, but it is now outperformed by the corresponding β-emitter agents (177)Lu-DOTATATE and (90)Y-DOTATOC. (131)I-MIBG is the radionuclide therapy of choice for inoperable or metastatic phaeochromocytomas/paragangliomas, which avidly concentrate this tracer via the noradrenaline transporter. Symptomatic, biochemical and tumour morphological response rates of 50-89%, 45-74% and 27-47%, respectively, have been reported. (131)I-MIBG is a second-line radiopharmaceutical for treatment of enterochromaffin carcinoids, mainly offering the benefit of amelioration of hormone-induced symptoms. High specific activity, non-carrier-added (131)I-MIBG and meta-astato((211)At)-benzylguanidine (MABG) are tracers with potential for enhanced therapeutic efficacy, yet their integration into clinical practice awaits further exploration. Amongst other promising agents, radiolabelled exendin analogues show potential for imaging and possibly therapy of insulinomas, while preclinical studies are currently evaluating DOTA peptides targeting the CCK-2/gastrin receptors that are overexpressed by medullary thyroid carcinoma cells.

Topics: 3-Iodobenzylguanidine; Carcinoid Tumor; Carcinoma, Neuroendocrine; Humans; Iodine Radioisotopes; Neuroendocrine Tumors; Octreotide; Paraganglioma; Pentetic Acid; Pheochromocytoma; Radiopharmaceuticals; Receptors, Somatostatin; Thyroid Neoplasms

Surgery is the only therapy able to cure patients with digestive neuroendocrine tumor. However, due to the presence of diffuse metastases, radical surgery is often not feasible. In these cases, medical treatment plays a critical role, because of its ability to control symptoms in functioning tumors and to inhibit tumor growth. Different therapeutic approaches, such as chemotherapy, hepatic artery chemoembolization and targeted radio-nuclide therapy can be used alone or combined to the biologic treatment with somatostatin analogues and interferon. However, an accurate staging by imaging procedures plus a histological, immunohistochemical and biomolecular examination must be performed before planning an optimal medical treatment.

Topics: Algorithms; Antineoplastic Agents, Hormonal; Carcinoid Tumor; Cell Differentiation; Combined Modality Therapy; Digestive System Neoplasms; Embolization, Therapeutic; Humans; Indium Radioisotopes; Neoplasm Proteins; Neoplasm Staging; Neuroendocrine Tumors; Octreotide; Pentetic Acid; Peptides, Cyclic; Receptors, Somatostatin; Retrospective Studies; Somatostatin; Treatment Outcome

Secondary tumours of any type in the breast are rare. A review of the literature demonstrated only 23 cases of carcinoid tumours with associated breast metastasis, as distinct from primary carcinoid tumours of the breast. Distant metastases from carcinoid tumours are correlated with poor prognosis and survival. Although both primary and metastatic mammary carcinoid tumours are uncommon, the recognition of the true origin of the tumours may be of importance owing to the different clinical management and prognosis of the two conditions. Recently, radionuclide-labelled imaging techniques have been applied to the localization of such lesions, based on isotope uptake by receptors present in these neuroendocrine tumours. We report two new cases of carcinoid tumours with breast metastases, the primaries being in the ileocaecal valve and the bronchus, respectively. The diagnosis of a carcinoid tumour was based on the clinical, biochemical, histopathological and immunostaining features. Furthermore, these patients had both 123I-MIBG and 111In pentetreotide scintigraphy performed. These radionuclides play a useful role in the localization and potentially in the management of carcinoid tumours and their distant metastases.

Topics: 3-Iodobenzylguanidine; Adult; Antineoplastic Agents; Breast Neoplasms; Bronchial Neoplasms; Carcinoid Tumor; Female; Humans; Ileal Neoplasms; Ileocecal Valve; Indium Radioisotopes; Iodine Radioisotopes; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals

Neuroendocrine tumors of the gastrointestinal tract are rare tumors that can be classified as APU-Domas (amine precursor uptake and decarboxylation). They can be subdivided into the carcinoid tumors of the gastrointestinal submucosa and the islet cell endocrine tumors of the pancreas. Although the majority of tumors that become clinically apparent are malignant, they are frequently slow growing. Despite this, neuroendocrine tumors may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better radiographic imaging and more accurate localization techniques. Medical therapies with somatostatin analogues, omeprazole, and locoregional tumor ablation have made a positive impact on curative and palliative therapy. This review updates the recent efforts made in the radiographic imaging and therapeutics of the gastrointestinal neuroendocrine tumors.

Topics: Adenoma, Islet Cell; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biogenic Amines; Carcinoid Tumor; Clinical Trials as Topic; Diagnostic Imaging; Embolization, Therapeutic; Gastrointestinal Neoplasms; Hepatic Artery; Humans; Indium Radioisotopes; Ligation; Liver Neoplasms; Octreotide; Palliative Care; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pentetic Acid; Receptors, Somatostatin

To evaluate the effectiveness of indium In 111 pentetate (diethylenetriaminepentaacetic acid [DTPA]-D-Phe-labeled octreotide scintigraphy in the localization of gastroenteropancreatic neuroendocrine lesions, and to identify covert lesions, determine multicentricity, define the distribution of metastases, confirm complete removal of tumor postoperatively, and evaluate the efficacy of therapeutic embolization.. Unmasked comparison.. Tertiary care referral center.. We studied 28 patients over a 12-month period. Biochemical evidence of a gastroenteropancreatic tumor was present in 13 patients. Octreoscan 111 was employed in four patients with an ambiguous biochemical diagnosis of gastroenteropancreatic tumor. Postoperative examination to document complete tumor removal was undertaken in seven patients. In one patient, Octreoscan 111 was used to evaluate the efficacy of therapeutic embolization.. [111In]DTPA-D-Phe-octreotide scintigraphy.. Identification of somatostatin receptor-bearing neuroendocrine tumors.. Intravenous administration of [111In]DTPA-D-Phe-octreotide followed by whole-body gamma camera scintigraphy resulted in the localization of gastroenteropancreatic neuroendocrine tumors with 75% sensitivity, 100% specificity, 100% positive predictive value, 63% negative predictive value, and 82% overall accuracy.. While Octreoscan 111 has been shown to localize the majority of amine precursor uptake and decarboxylation system (APUD) cell tumors as well as various other somatostatin-positive tumors, this technique may also be useful in a number of other circumstances. These include prediction of tumors that will respond to octreotide therapy, identification of covert metastases, intraoperative identification of tumors, and postoperative surveillance. Use of an alternative isotope may provide a vehicle for the administration of local therapeutic radiation to tumor cells. The precise efficacy of Octreoscan 111 in the identification of lesions smaller than 3 cm with low-density somatostatin-2 receptor expression remains to be determined.

Topics: Adult; Aged; Carcinoid Tumor; Duodenal Neoplasms; Female; Gastrinoma; Humans; Indium Radioisotopes; Insulinoma; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity; Stomach Neoplasms

In this review, we evaluate radiological techniques currently used to localize gastroenteropancreatic (GEP) endocrine tumors. We also describe the visualization, using intravenous administration of two isotope-labelled somatostatin analogs (123-I-Tyr3-octreotide and 111In-DTPA-octreotide), of islet cell tumors in 25 patients and carcinoids in 39 patients. The primary tumor as well as previously unrecognized distant metastases were visualized in 20 of the 25 patients (80%) and in 37 of the 39 (95%). Parallel in vitro detection of somatostatin receptors on those tumors also visualized in vivo showed that ligand binding to the tumor in vivo represents binding to specific somatostatin receptors. The detection of somatostatin receptors on tumors in vivo predicted a good suppressive effect of octreotide on hormonal hypersecretion by these tumors. It is an easy, quick and harmless procedure, valuable in the localization of primary endocrine pancreatic tumors and their often radiologically and clinically unrecognized metastases. Future prospective controlled studies comparing this procedure with other radiological investigative techniques should demonstrate its sensitivity and specificity and determine the place of somatostatin receptor imaging in the localization of GEP endocrine tumors.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Diagnostic Imaging; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Iodine Radioisotopes; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Receptors, Somatostatin

To evaluate the diagnostic sensitivity and accuracy and the cost-effectiveness of this technique in the detection of gastroenteropancreatic carcinoid tumors and their metastases in comparison with conventional imaging methods.. Somatostatin receptor scintigraphy (SRS) was performed in 24 patients with confirmed carcinoids and 7 under investigation. The results were compared with those of conventional imaging methods (chest X-ray, upper abdominal ultrasound, chest CT, upper and lower abdominal CT). Also a cost-effectiveness analysis was performed comparing the cost in Euro of several combinations of SRS with conventional imaging modalities.. SRS visualized primary or metastatic sites in 71.0% of cases and 61.3% of conventional imagings. The diagnostic sensitivity of the method was higher in patients with suspected lesions (85.7% vs 57.1%). SRS was less sensitive in the detection of metastatic sites (78.9% vs 84.2%). The undetectable lesions by SRS metastatic sites were all in the liver. Between several imaging combinations, the combinations of chest X-ray/upper abdominal CT/SRS and chest CT/upper abdominal CT/SRS showed the highest sensitivity (88.75%) in terms of the number of detected lesions. The combinations of chest X-ray/upper abdominal US/SRS and chest CT/upper abdominal ultrasound /SRS yielded also a quite similar sensitivity (82%). Compared to the cost of the four sensitive combinations the combination of chest X-ray/upper abdominal ultrasound/SRS presented the lower cost, 1183.99 Euro vs 1251.75 Euro for chest CT/upper abdominal ultrasound/SRS, 1294.93 Euro for chest X/ray/upper abdominal CT/SRS and 1362.75 Euro for chest CT/upper abdominal CT/SRS.. SRS imaging is a very sensitive method for the detection of gastroenteropancreatic carcinoids but is less sensitive than ultrasound and CT in the detection of liver metastases. Between several imaging combinations, the combination of chest X-ray/upper abdominal CT/SRS shows the highest sensitivity with a cost of 1294.93 Euro.

Topics: Adult; Aged; Carcinoid Tumor; Cost-Benefit Analysis; Female; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity

To report our experience with both (123)I-vasoactive intestinal peptide (VIP) and (111)In-DTPA-D-Phe(1)-octreotide for imaging to identify primary and metastatic tumor sites in carcinoid patients.. One hundred ninety-four patients with a verified or clinically suspected diagnosis of a carcinoid tumor were injected with (111)In-DTPA-D-Phe(1)-OCT for imaging purposes, while 133 patients underwent scanning with both (123)I-VIP and (111)In-DTPA-D-Phe(1)-OCT in random order. Imaging results were compared with computed tomography scans, results of conventional ultrasound, endosonography, and endoscopy, and results of surgical exploration in case of inconclusive conventional imaging.. Primary or recurrent carcinoid tumors could be visualized with (111)In-DTPA-D-Phe(1)-OCT in 95 (91%) of 104 patients; metastatic sites were identified in 110 (95%) of 116 patients. In 11 (51%) of 21 patients with suggestive symptoms but without identified lesions by conventional imaging, focal tracer uptake located the carcinoid tumor. In addition, metastatic disease was demonstrated in three patients after resection. In a direct comparison in the 133 patients who underwent both imaging modalities, (111)In-DTPA-D-Phe(1)-OCT was found to be superior to (123)I-VIP, with 35 (93%) of 38 versus 32 (82%) of 38 scans being positive in primary or recurrent tumors, 58 (90%) of 65 versus 53 (82%) of 65 being positive in patients with metastatic sites, and seven (44%) of 16 versus four (25%) of 16 being positive in patients with symptoms but otherwise negative work-ups. Overall, additional lesions not seen on conventional imaging were imaged in 43 (41%) of 158 versus 25 (25%) of 103 scans with (111)In-DTPA-D-Phe(1)-OCT and (123)I-VIP, respectively.. Both peptide tracers have a high sensitivity for localizing tumor sites in patients with ascertained or suspected carcinoid tumors, with (111)In-DTPA-D-Phe(1)-OCT scintigraphy being more sensitive than (123)I-VIP receptor scanning. Both, however, had a higher diagnostic yield than conventional imaging, as verified by surgical intervention or long-term follow-up. The combination of both peptide receptor scans does not seem to further enhance diagnostic information.

Topics: Adult; Aged; Carcinoid Tumor; Humans; Indium Radioisotopes; Iodine Radioisotopes; Middle Aged; Octreotide; Pentetic Acid; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Vasoactive Intestinal Peptide

Disseminated neuroendocrine tumours are difficult to treat and are generally not responsive to radiotherapy or chemotherapy. Nuclear medicine techniques using a radiolabelled somatostatin analogue, 111In-Octreotide, have been used for the diagnosis of neuroendocrine tumours. It has been suggested that high activities of such an agent may have a therapeutic effect. The aims of this study were to assess toxicity and to determine if there had been evidence of efficacy. Eight patients with known disseminated neuroendocrine tumours were enrolled in the study; six had carcinoid tumours, one had a medullary cell carcinoma of the thyroid and one patient had a malignant gastrinoma. Between 1.3 and 4.6 GBq of 111In-Octreotide were administered to each patient for up to five administrations over 12 months. A total of 23 administrations were given. Tests of vital signs, renal, liver and endocrine function as well as haematological markers were taken before and after treatment. The treatment was well tolerated with only one patient suffering from a sensation of flushing during the infusion but no changes in vital sings. There was a transient (up to 48 h) drop in circulating lymphocytes in four patients and platelets in two patients; no supportive therapy was needed. One patient with severe renal impairment had a slight reduction in glomerular filtration rate. We conclude that high-activity 111In-Octreotide is well tolerated with low toxicity and can be considered for use in patients with disseminated neuroendocrine tumours. Further work is now being performed to assess efficacy.

Topics: Adult; Aged; Bone and Bones; Carcinoid Tumor; Female; Gastrinoma; Glomerular Filtration Rate; Humans; Lymphocyte Count; Male; Middle Aged; Multiple Endocrine Neoplasia; Neuroendocrine Tumors; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals

Scintigraphy with somatostatin analogs is a sensitive method for the staging and therapeutic management of patients with endocrine gastroenteropancreatic (GEP) tumors. The aim of this study was to compare prospectively somatostatin receptor scintigraphy (SRS) using 111n-pentetreotide with bone scintigraphy using 99mTc-hydroxymethylene diphosphonate for the detection of bone metastases.. One-hundred-forty-five patients with proven endocrine GEP tumors were investigated. Patients were classified according to the presence of bone metastases as indicated by CT, MRI or histologic data. Group I included 19 patients with confirmed bone metastases, and group II included 126 patients without bone metastases.. In group I, SRS was positive in all 19 patients with bone metastases, and bone scintigraphy was positive in 17 patients. Bone metastases were found to occur predominantly in patients with liver metastases. In group 11, 5 patients had recent bone surgery for fracture or arthritis. SRS showed bone uptake in 4 of these patients, and bone scanning showed abnormal uptake in 5. In 7 of the remaining 121 group II patients, SRS was negative and bone scanning showed abnormal bone uptake suggesting bone metastases. The detection of bone metastases was of major prognostic value, because 42% of group 1 patients died during a 2-y follow-up.. In patients with GEP tumors, the accuracy of SRS appears to be similar to that of bone scintigraphy for the detection of bone metastases.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Carcinoid Tumor; Digestive System Neoplasms; Female; Humans; Indium Radioisotopes; Male; Middle Aged; Octreotide; Pentetic Acid; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Technetium Tc 99m Medronate; Zollinger-Ellison Syndrome

Several authors proposed the stage at diagnosis and some histopathological features as prognostic factors of bronchial carcinoids. However, since large tumour diameters or nodal metastases are frequently associated to aggressive histology, their prognostic role is unclear. To investigate the relationships between the clinicopathological parameters at diagnosis and outcome, 21 patients were analysed. Overall 26% of the radically resected patients recurred. Recurrences and disease-specific mortality were related to atypical histology and, only in cases with typical histology, to the presence of hilar or mediastinal lymph node metastases. These prognostic factors were valuable independently of the size of the primary tumour, that was remarkably homogeneous, always less than 3 cm, thus not predictive of recurrence. Moreover we evaluated the role of somatostatin receptor scintigraphy, a diagnostic tool only preliminary studied in this field. Scintigraphy with 111In-octreotide revealed the primary tumours at diagnosis (8/8), the increase in tumour size in two unresected patients, and all the cases of recurrent or metastatic disease (5/11), sometimes before the appearance of symptoms. These results suggest the usefulness of histology and nodal status as prognostic factors in clinical practice. Somatostatin receptor scintigraphy turns out to be a powerful diagnostic tool, for an accurate staging and an early diagnosis of recurrence in bronchial carcinoids.

Topics: Adult; Aged; Bronchial Neoplasms; Carcinoid Tumor; Female; Follow-Up Studies; Humans; Indium Radioisotopes; Male; Middle Aged; Octreotide; Pentetic Acid; Prognosis; Radionuclide Imaging

After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors.

Topics: Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Intraoperative Care; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Stomach Neoplasms; Thyroid Neoplasms; Uterine Cervical Neoplasms

To evaluate the effectiveness of indium In 111 pentetate (diethylenetriaminepentaacetic acid [DTPA]-D-Phe-labeled octreotide scintigraphy in the localization of gastroenteropancreatic neuroendocrine lesions, and to identify covert lesions, determine multicentricity, define the distribution of metastases, confirm complete removal of tumor postoperatively, and evaluate the efficacy of therapeutic embolization.. Unmasked comparison.. Tertiary care referral center.. We studied 28 patients over a 12-month period. Biochemical evidence of a gastroenteropancreatic tumor was present in 13 patients. Octreoscan 111 was employed in four patients with an ambiguous biochemical diagnosis of gastroenteropancreatic tumor. Postoperative examination to document complete tumor removal was undertaken in seven patients. In one patient, Octreoscan 111 was used to evaluate the efficacy of therapeutic embolization.. [111In]DTPA-D-Phe-octreotide scintigraphy.. Identification of somatostatin receptor-bearing neuroendocrine tumors.. Intravenous administration of [111In]DTPA-D-Phe-octreotide followed by whole-body gamma camera scintigraphy resulted in the localization of gastroenteropancreatic neuroendocrine tumors with 75% sensitivity, 100% specificity, 100% positive predictive value, 63% negative predictive value, and 82% overall accuracy.. While Octreoscan 111 has been shown to localize the majority of amine precursor uptake and decarboxylation system (APUD) cell tumors as well as various other somatostatin-positive tumors, this technique may also be useful in a number of other circumstances. These include prediction of tumors that will respond to octreotide therapy, identification of covert metastases, intraoperative identification of tumors, and postoperative surveillance. Use of an alternative isotope may provide a vehicle for the administration of local therapeutic radiation to tumor cells. The precise efficacy of Octreoscan 111 in the identification of lesions smaller than 3 cm with low-density somatostatin-2 receptor expression remains to be determined.

Topics: Adult; Aged; Carcinoid Tumor; Duodenal Neoplasms; Female; Gastrinoma; Humans; Indium Radioisotopes; Insulinoma; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity; Stomach Neoplasms

In the present study we have investigated the three-dimensional (3D) reconstruction of OctreoScan111 SPECT (single photon emission tomography) images in 20 patients with neuroendocrine tumours. All patients had at least 2 tumour lesions as assessed from computerized tomography (CT) and SPECT. The 3D rendering was performed using a software, which produces images by implementing direct rendering from voxels without an intermediate surface data structure. The software has options for a free choice of thresholding and possibilities of clipping in coronal, transversal and sagittal planes. The results obtained showed that 3D reconstruction with volume rendering (3Dvr) gave a superior topographical localization of tumour uptakes when compared with SPECT. The 3Dvr technique was also combined with transversal clipping in rendered volumes (3Dvr+c). The major advantage with the 3Dvr+c technique was found to be an improved visualization of anatomical references as well as improved diagnostic information in a particular, selected, transversal slice, thus facilitating the identification and comparison of individual tumour lesions.

Topics: Abdominal Neoplasms; Carcinoid Tumor; Female; Humans; Image Processing, Computer-Assisted; Indium Radioisotopes; Intestinal Neoplasms; Male; Neoplasms; Neurosecretory Systems; Octreotide; Pentetic Acid; Tomography, Emission-Computed, Single-Photon

In order to evaluate the diagnostic reliability of somatostatin receptor scintigraphy (SRS) in patients treated with somatostatin analogs, ten patients with metastatic neuroendocrine tumors were investigated before and during continuous treatment. Different somatostatin analogs were used for therapy: five patients received octreotide (Sandostatin, Sandoz, Switzerland) and five were treated with BIM 23014 (Lanreotide, Ipsen Biotech, France) within the scope of a clinical phase II study. The SRS findings were analyzed in terms of biodistribution of the labeled somatostatin analog and tumor visualization comparing the two studies in each patient. Whereas liver, spleen, and kidney uptake were decreased during octreotide treatment and increased on lanreotide therapy, tumor accumulation was intensified in all but one patient. Our results suggest that the diagnostic value of SRS is not necessarily restricted during treatment with somatostatin analogs. Indeed, tumor visualization may even be enhanced in this therapeutic setting.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Liver Neoplasms; Male; Metabolic Clearance Rate; Middle Aged; Octreotide; Pentetic Acid; Peptides, Cyclic; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin; Technetium Tc 99m Medronate; Tissue Distribution

Topics: ACTH Syndrome, Ectopic; Adult; Bronchial Neoplasms; Carcinoid Tumor; Cushing Syndrome; Diagnosis, Differential; Humans; Indium Radioisotopes; Male; Octreotide; Pentetic Acid; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Carcinoid Tumor; Child; Female; Humans; Image Enhancement; Male; Middle Aged; Neoplasm Staging; Octreotide; Organotechnetium Compounds; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET. GRS was directly compared with SRS. If lesions were visible on GRS but not detectable by SRS, other imaging modalities (MRI, CT) and follow-up were used for verification. Of the 60 evaluable patients, 51 had carcinoid tumours, 3 gastrinomas, 2 glucagonomas, 1 insulinoma and 3 paragangliomas. The overall tumour-detection rate was 73.7% for GRS and 82.1% for SRS. In the 11 patients with negative SRS, GRS was positive in 6 (54.5%). Based on the number of tumour sites detected and the degree of uptake, GRS performed better than SRS in 13 patients (21.7%), equivalent images were obtained in 18 cases (30.0%) and SRS performed better in 24 (40.0%) cases. In six of the SRS positive patients, 18 additional sites of tumour involvement could be detected. Overall, GRS detected additional tumour sites in 20% of the patients. Localisation of the primary tumours or their functional status had no influence on the outcome of imaging. GRS should be performed in selected patients as it may provide additional information in patients with NET with equivocal or absent somatostatin uptake.

Topics: Adult; Aged; Carcinoid Tumor; Diagnosis, Differential; Female; Glucagonoma; Humans; Indium Radioisotopes; Insulinoma; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Paraganglioma; Pentetic Acid; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Receptor, Cholecystokinin B; Receptors, Somatostatin

We report a case of a rectal carcinoid tumor that was treated using endoscopic resection. This case highlights the usefulness of using somatostatin receptor scintigraphy in the postresection endoscopy of the tumor and the intraoperative use of a gamma probe detector for the surgical resection of metastatic adenopathy that had not been detected using computed tomography (CT) scanning.. The patient was studied using CT scanning, somatostatin receptor scintigraphy (SRS), and rectal endoscopic ultrasonography (EUS). A gamma probe detector was scheduled for use during the subsequent surgical intervention.. The SRS demonstrated a pelvic metastatic lymphatic node that had not been detected on CT scanning. Additional EUS did not show regional metastatic lymph nodes. Histopathology following removal of retroperitoneal and presacral lymphatic nodes confirmed the diagnosis of metastatic carcinoid tumor. At follow up at 6 months, SRS and rectoscopy were normal.. Somatostatin receptor scintigraphy is very useful in identifying the presence of lymph node metastases, even with a small rectal carcinoid tumor. This is of considerable importance when scheduling surgery and the CT and EUS are normal. The use of an intraoperative gamma-probe detector assists in the surgical excision of the metastatic lymphatic nodes, especially because they had been detected only using SRS, and when their exact location is uncertain.

Topics: Carcinoid Tumor; Female; Gamma Cameras; Humans; Intraoperative Care; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Rectal Neoplasms; Surgery, Computer-Assisted

Malignant carcinoid tumors express high numbers of somatostatin receptors. Radiation therapy using labeled somatostatin analogs is a novel treatment modality for these tumors. We have analyzed the biokinetics and therapeutic effect of radiolabeled somatostatin analog on a human midgut carcinoid grafted to nude mice. A transplantable human midgut carcinoid (GOT1) was grafted to the back of nude mice. Tumor-bearing mice were injected with (111)In-DTPA-D-Phe(1)-octreotide, followed by measurement of (111)In activity concentration ratios in tumor tissues. Tumor-bearing mice were also injected with (177)Lu-DOTA-Tyr(3)-octreotate and followed for 7 days. The concentration of (111)In-DTPA-D-Phe(1)-octreotide in tumor tissues was very high 4 hours postinjection with 0.4-13% of injected activity per gram. Injection of 30-120 MBq (177)Lu-DOTA-Tyr(3)-octreotate reduced tumor volume to 7-14% of the original tumor volume 7 days postinjection. Microscopic analysis of treated tumors revealed widespread areas of tumor cell necrosis and fibrosis. It was found that grafted GOT1 cells to nude mice represent an authentic model for studying human midgut carcinoids. Radiolabeled somatostatin analogs have a high selectivity for tumor tissue and can induce tumor cell necrosis. Radiotherapy of carcinoid tumors with (177)Lu-DOTA-Tyr(3)-octreotate appears to be a promising treatment modality for either palliative treatment or completion therapy after attempted surgical cure.

Topics: Animals; Carcinoid Tumor; Disease Models, Animal; Indium Radioisotopes; Mice; Mice, Nude; Neoplasm Transplantation; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Xenograft Model Antitumor Assays

In nude mice carrying the human carcionoid GOT1 different amounts of (111)In-DTPA-Phe(1)-octreotide and routes of administration were studied in relation to uptake in tumor and normal organs. The relative organ uptake varied with given amount; highest in tumor after 0.1 and 1 microg and lowest in muscle, heart and blood after 0.1 microg. The uptake decreased in lungs and spleen with higher amounts of (111)In-DTPA-Phe(1)-octreotide. In all organs studied the tumor-to-normal-tissue activity concentration ratio was maximal at 0.1 and 1 microg, but route of administration influenced the uptake only little.

Topics: Animals; Carcinoid Tumor; Humans; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Male; Mice; Mice, Inbred BALB C; Octreotide; Pentetic Acid; Radiopharmaceuticals

We performed this study in order to evaluate the diagnostic accuracy of whole-body fluorodeoxyglucose positron emission tomography (FDG PET) imaging and somatostatin receptor scintigraphy (SRS) for localizing primary carcinoid tumours and evaluating the extent of the disease. A secondary aim was to correlate those findings with the histological characteristics of the lesions. FDG PET was performed in 17 patients and SRS in 16. All patients had pathologically proven carcinoids. All lesions were verified by histopathological analysis or by follow-up. Ki-67 and p53 expression were assessed as an indicator of the tumours' aggressiveness. FDG PET correctly identified 4/7 primary tumours and 8/11 metastatic spreads, as compared to six and 10 respectively, for SRS. Most tumours were typical carcinoids with low Ki-67 expression. No correlation was found between the histological features and the tracer's uptake. We conclude that SRS remains the modality of choice for evaluating patients with carcinoid tumours, regardless of their proliferative activity. FDG PET should be reserved to patients with negative results on SRS.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoid Tumor; False Negative Reactions; Female; Fluorodeoxyglucose F18; Humans; Ki-67 Antigen; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Single-Blind Method; Statistics as Topic; Tumor Suppressor Protein p53

Topics: Aged; Carcinoid Tumor; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Ileal Neoplasms; Indium Radioisotopes; Jejunal Neoplasms; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Proteins; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Tomography, X-Ray Computed

This study aimed to evaluate the diagnostic utility of 111In-DTPA-D-Phe1-octreotide scintigraphy in the different situations that can be present when an examination is requested during the clinical course of the carcinoid tumor (CT).. We have performed 41 scintigraphies with 111In-octreotide (145-185 MBq) in 35 patients (19 females and 16 males) with clinically suspected or confirmed CT. The patients were classified into five groups: Group A: Indolent symptoms of CT (n=9); B: CT staging located in lung (n=4), stomach (n=2), cecum (n=1), thymus (n=1) and pancreas (n=1); C: Carcinoid syndrome (n=1); D: CT staging after surgery located in pancreas (n=1), ovary (n=1), cecum (n=1), stomach (n=1), appendix (n=1) and ileum (n=1); and E: Post-treatment follow-up (n=13), with CT located in bronchial tree (n=5), small intestine (n=3), appendix (n=2), thymus (n=1), ovary (n=1) and unknown primary tumor (n=1). Three patients of this group had one scintigraphic study before the treatment. Head and neck, thorax and abdomen images were obtained at 4 and 24 h in all of the patients and SPECT images of the abdomen (n=14), thorax (n=10), and brain (n=1) were obtained at 24 h in 25 patients.. Group A: In the 3 patients with a positive scintigraphy, the definitive diagnosis was meningioma, Hurtle cell's carcinoma and lung adenocarcinoma. The clinical follow-up in the six other patients, at least during one year, did not show any evidence of CT. Group B: Six of the 9 CT were detected with the scintigraphy. In 2 cases of bronchial CT, the scan showed sarcoidotic regional lymph node involvement and CT hepatic and bone metastases, respectively. Group C: The scintigraphy detected hepatic metastases from an unknown primary tumor. Group D: The scintigraphy was positive in 3 cases (hepatic or/and abdominal metastases) and was normal in the other 3. The scintigraphy was negative in one patient with peritoneal metastases. Group E: The scintigraphy was normal in 7 patients in concordance with the clinical follow-up. In 3 patients with a scintigraphy performed prior to treatment, the scintigraphy detected recurrence (thymic CT), progression of the metastatic disease (ovarian CT) and partial regression of the hepatic metastases (carcinoid syndrome). In the three other patients, the scintigraphy showed metastases located in liver in one patient and hepatic and extra-hepatic metastases in the two other patients. The sensitivity and specificity of 111In-Octreotide in the detection of the primary tumor and metastases were 72% and 84% respectively.. The 111In-Octreotide scintigraphy has a low diagnostic utility in patients with indolent symptoms of CT. However, it is the first line of diagnosis for the staging of the CT and to evaluate the follow up after therapy.

Topics: Adult; Aged; Bone Neoplasms; Brain Neoplasms; Carcinoid Tumor; Diagnosis, Differential; Digestive System Neoplasms; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Proteins; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Sarcoidosis; Thymus Neoplasms; Thyroid Neoplasms; Tomography, Emission-Computed, Single-Photon

The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe(1)-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe(1)-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe(1)-octreotide (0.1 microg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe(1)-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues.

Topics: Animals; Carcinoid Tumor; Humans; Injections, Intravenous; Male; Mice; Mice, Nude; Neoplasm Transplantation; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution

64Cu (half-life, 12.7 h; beta+, 0.653 MeV [17.4%]; beta-, 0.579 MeV [39%]) has shown potential as a radioisotope for PET imaging and radiotherapy. (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide (OC) was developed for imaging somatostatin-receptor-positive tumors using conventional scintigraphy. With the advantages of PET over conventional scintigraphy, an agent for PET imaging of these tumors is desirable. Here, we show that 64Cu-TETA-OC (where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid) and PET can be used to detect somatostatin-receptor-positive tumors in humans.. Eight patients with a history of neuroendocrine tumors (five patients with carcinoid tumors and three patients with islet cell tumors) were imaged by conventional scintigraphy with (111)In-DTPA-OC (204-233 MBq [5.5-6.3 mCi]) and by PET imaging with 64Cu-TETA-OC (111 MBq [3 mCi]). Blood and urine samples were collected for pharmacokinetic analysis. PET images were collected at times ranging from 0 to 36 h after injection, and the absorbed doses to normal organs were determined.. In six of the eight patients, cancerous lesions were visible by both (111)In-DTPA-OC SPECT and 64Cu-TETA-OC PET. In one patient, (111)In-DTPA-OC showed mild uptake in a lung lesion that was not detected by 64Cu-TETA-OC PET. In one patient, no tumors were detected by either agent; however, pathologic follow-up indicated that the patient had no tumors. In two patients whose tumors were visualized with (111)In-DTPA-OC and 64Cu-TETA-OC, 64Cu-TETA-OC and PET showed more lesions than (111)In-DTPA-OC. Pharmacokinetic studies showed that 64Cu-TETA-OC was rapidly cleared from the blood and that 59.2% +/- 17.6% of the injected dose was excreted in the urine. Absorbed dose measurements indicated that the bladder wall was the dose-limiting organ.. The high rate of lesion detection, sensitivity, and favorable dosimetry and pharmacokinetics of 64Cu-TETA-OC indicate that it is a promising radiopharmaceutical for PET imaging of patients with neuroendocrine tumors.

Topics: Adenoma, Islet Cell; Aged; Animals; Carcinoid Tumor; Female; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Papio; Pentetic Acid; Radiation Dosage; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Tomography, Emission-Computed

Topics: Antineoplastic Agents, Hormonal; Buttocks; Carcinoid Tumor; Female; Granuloma; Humans; Injections, Intramuscular; Middle Aged; Muscle, Skeletal; Muscular Diseases; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals

Surgery is the treatment of choice for bronchial carcinoid tumor (BCT), whenever the staging is adequate. There is little information about the capability of the somatostatin receptor scintigraphy (SRS) to detect bone metastases in the carcinoid tumor.. This work has aimed to evaluate retrospectively the diagnostic accuracy of the SRS in the detection of bone metastases in BCT.. Based on their clinical indication, the patients were classified into two different groups: Group A (n = 4), staging of a known BCT; and Group B (n = 6), treatment control. The SRS results could be correlated with the CT results in all 4 patients from the group A, and in one patient from the group B, and the SRS results were compared with the clinical follow up during at least one year in the other 5 patients.. The SRS scan detected the 4 BCT from the group A; in 2 of them the patient staging was superior when the SRS was used than with the CT, whereas the scan overestimated the tumor stage (BCT + sarcoidosis) in another patient. During the clinical course, one of these patients developed bone and liver metastases. The SRS was normal in 5 asymptomatic patients from group B, whereas the scan showed disseminated metastatic disease (liver, bone, spleen and lymph nodes) in another patient. In the 2 patients with bone metastases, the total number of bone metastases detected by the bone scan was 12, and by the SRS 8. The four lesions that were not detected by SRS were located in the ribs (n = 3) and 12-D (n = 1).. The capability of the SRS to detect bone metastases makes it more useful in BCT staging. Over the next few years, the role of the bone scan and SRS in the detection of bone metastases in carcinoid tumors needs to be established.

Topics: Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Bronchial Neoplasms; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Proteins; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Retrospective Studies; Technetium Tc 99m Medronate; Tomography, Emission-Computed, Single-Photon

Treatment with tumor-targeting substances is currently being evaluated in clinical trials. For patients with neuroendocrine tumors expressing somatostatin receptors, the 111In-labeled somatostatin analog [diethylenetriaminepentaacetic acid (DTPA)-DPhe1]-octreotide has been used with promising results. To further investigate the clinical effect of the injected conjugate, we analyzed the cellular distribution of 111In by ultrastructural autoradiography.. Seven patients with somatostatin receptor-expressing midgut carcinoid tumors scheduled for abdominal surgery were investigated by somatostatin receptor scintigraphy. During operation, tumor tissue samples and samples of normal intestine were collected, fixed, and processed for electron microscopy. A thin layer of film emulsion was applied on sections and after the exposure film was developed. The cellular distribution of silver precipitations indicating the presence of isotope was evaluated.. Cell surface receptor binding and internalization of [111In-DTPA-D-Phe1]-octreotide in the tumor cells was easily revealed by silver precipitations in the film. Multiple silver grains were seen at the plasma membrane, in the cytoplasmic area among secretory granules and vesicular compartments, and in the perinuclear area. Silver grains were also regularly located in the nucleus. For all patients, the silver precipitation patterns from 111In decay were identical in all examined cells from removed tumors, and in most cells 111In could be seen in the nucleus. The specificity of the silver reaction products is supported by the observation that enterocytes in intestinal tissue specimens from near the tumor did not show any silver grains and no background labeling was seen in the plastic.. After internalization through the somatostatin receptor system, 111In is translocated to the perinuclear area and into the nucleus. Whether the nuclide is still conjugated to the intact somatostatin analog or to part of it cannot be evaluated in this study. Despite the short irradiation range of 111In, the nuclear localization can explain its clinical effectiveness. The results from this study suggest that [111In-DTPA-D-Phe1]-octreotide may act as a powerful tumor cell-targeting substance.

Topics: Adult; Aged; Autoradiography; Carcinoid Tumor; Cell Membrane; Cell Nucleus; Cytoplasm; Female; Humans; Indium Radioisotopes; Intestinal Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Tomography, Emission-Computed, Single-Photon

Gastric carcinoids are of increasing clinical concern because they may develop in hypergastrinemic states, especially with the increased chronic use of potent acid suppressants that can cause hypergastrinemia. However, gastric carcinoids are difficult to diagnose. Somatostatin receptor scintigraphy (SRS) has a high sensitivity and specificity for localizing carcinoids in other locations. The purpose of this study was to determine whether SRS could localize gastric carcinoids.. Two groups of patients with Zollinger-Ellison syndrome (ZES) with hypergastrinemia, each having a different increased risk of developing gastric carcinoids, were studied. One hundred sixty-two consecutive patients with ZES were studied prospectively, with 39 having multiple endocrine neoplasia, type 1 (MEN-1) (high increased risk), and 123 not having MEN-1 (low increased risk). Patients were admitted to the hospital initially and then yearly, undergoing SRS with SPECT, upper gastrointestinal endoscopy, and Jumbo Cup biopsies of any gastric abnormalities, as well as random biopsies of the gastric body. Tumor localization studies were also performed. Both the results of the routine SRS interpretation and the results of a masked review, with particular attention to the stomach of high risk MEN-1 patients, were correlated with the gastric biopsy results.. Gastric SRS localization was positive in 19 (12%) of 162 patients. Sixteen patients had a gastric carcinoid, and 12 of these patients had SRS localization. The sensitivity of SRS in localizing a gastric carcinoid was 75%, with a specificity of 95%. Positive and negative predictive values were 63% and 97%, respectively.. SRS is a noninvasive method that can identify patients with gastric carcinoids with a reasonable sensitivity and a high specificity. SRS should prove useful in the treatment of patients with hypergastrinemic states that have an increased incidence of gastric carcinoids. In patients with MEN-1, one must realize that localization in the upper abdomen on SRS may be caused by a gastric carcinoid and not a pancreatic endocrine tumor.

Topics: Carcinoid Tumor; Case-Control Studies; Female; Humans; Indium Radioisotopes; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Octreotide; Pentetic Acid; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Stomach Neoplasms; Tomography, Emission-Computed, Single-Photon; Zollinger-Ellison Syndrome

Radioactive tumor targeting agents are highly interesting and for treatment of neuroendocrine tumors expressing somatostatin receptors, radiolabeled somatostatin analogues (including [(111)In-DTPA-D-Phe1]-octreotide) has been tried in a small number of patients with encouraging results. To increase our knowledge about the in vivo processing of administered [(111)In-DTPA-D-Phe1]-octreotide we have examined tumor and normal tissue material from a patient with a midgut carcinoid tumor. By ultrastructural autoradiography, silver grains indicating the presence of [(111)In-DTPA-D-Phe1]-octreotide could be identified within tumor cells, both in the primary tumor and in the mesenteric metastases. Silver grains were also found in leukocytes and in blood vessels. However, normal enterocytes did not show any specific radioligand uptake. This study indicates that the binding and endocytosis of [(111)In-DTPA-D-Phe1]-octreotide is a specific process that takes place in cells expressing somatostatin receptors. However, the importance of the number of somatostatin receptors and subtypes expressed will have to be further studied.

Topics: Animals; Carcinoid Tumor; CHO Cells; Cricetinae; Endocytosis; Indium Radioisotopes; Intestinal Neoplasms; Ligands; Octreotide; Pentetic Acid; Receptors, Somatostatin; Tomography, Emission-Computed, Single-Photon; Transfection; Tumor Cells, Cultured

Bronchial carcinoid (BC) is a rare etiology of Cushing syndrome, and difficulties in differential diagnosis with Cushing's disease are often present. We report two cases in which octreotide scintigraphy was an important diagnostic tool. The first patient showed a 1 cm non-specific pulmonary nodule on CT scan that was positive on scintigraphy, being confirmed by surgery. The second case was a man that had been operated but not cured of an ACTH secreting BC that continued with high ACTH levels and negative localization imaging studies. A subsequent scintigraphy showed a positive image suggestive of recurrence. Octreotide scintigraphy may be considered in patients with suspicion of ectopic ACTH syndrome although a positive image in CT scan be present.

Topics: Aged; Bronchial Neoplasms; Carcinoid Tumor; Cushing Syndrome; Female; Humans; Male; Middle Aged; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals

Many tumors with neuroendocrine characteristics express high amounts of somatostatin receptors that enable in vivo imaging with [(111)In-DTPA-D-Phe1]-octreotide. In this study, we have analyzed the feasibility in detecting and characterizing thymic masses by somatostatin receptor scintigraphy (SRS).. Eighteen patients (13 women, 5 men, ages 18-78 yr; mean +/- s.d. = 42.1 +/- 17.6 yr) were enrolled in this study. Eleven patients were studied during diagnosis and seven during routine follow-up. In seven patients, myasthenia gravis was the presenting symptom. SRS was performed within 4 wk after CT and/or MRI. Planar and tomographic images were acquired within 24 hr after the injection of approximately 111 MBq of [(111)In-DTPA-D-Phe1]-octreotide. The scintigraphic results were categorized according to the histologic findings.. Histology diagnosed 10 mixed epithelial/lymphoid thymomas (8 with prevalent epithelial component), 2 thymic carcinomas, 1 thymic carcinoid, 1 lymphangioma and 4 thymic hyperplasias. Two thymoma were Stage I, 3 were Stage II, 2 were Stage III and 5 were Stage IV, as was the thymic carcinoid. Indium-111-DTPA-D-Phe1-octreotide concentrated in primary and/or metastatic sites of thymic tumors, thereby enabling successful external gamma imaging of sites greater than 1.5 cm in size. Tumor-to-lung (T/L) ratios were as high as 7.6-fold (range 1.7-7.6). Untreated thymomas showed higher T/L (4.34 +/- 1.57) than treated ones (2.68 +/- 1.18). No uptake was detectable in the four patients with benign thymic hyperplasia and the patient with the lymphangioma.. Indium-111-DTPA-D-Phe1-octreotide is avidly concentrated within thymic tumors, but it is not concentrated by thymic hyperplasia, which allows differential diagnosis. Thus, in patients with myasthenia gravis, SRS may have a role in characterizing thymic masses, thereby overcoming the limits of cross-sectional imaging modalities.

Topics: Adolescent; Adult; Aged; Carcinoid Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Octreotide; Pentetic Acid; Radiopharmaceuticals; Thymoma; Thymus Hyperplasia; Thymus Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

We describe two cases of bronchial carcinoid tumour detected by (111In-DTPA-D-Phe1)-octreotide scintigraphy. The SPECT of the thoratic region provided a better images of the primary tumour than the planar images. In one of the patients, the bronchial carcinoid tumour was associated with sarcoidosis, which led to an erroneous evaluation of the extension of the tumour.

Topics: Adult; Biopsy; Bronchi; Bronchial Neoplasms; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Lung; Lung Diseases; Lymphatic Diseases; Middle Aged; Octreotide; Pentetic Acid; Radiography, Thoracic; Radiopharmaceuticals; Sarcoidosis; Terbium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The differential diagnosis and management of Cushing's syndrome remain difficult, particularly for ectopic adrenocorticotropin (ACTH) syndromes resulting from small bronchial carcinoids. We report the case of a 41-year-old man with ectopic ACTH-dependent Cushing's syndrome. Two computed tomography scans of the thorax were normal and magnetic resonance imaging of the chest showed a 6-mm hyperintense T1-weighted area close to the left pulmonary hilus, interpreted as probably vascular by the radiologists. An [111In-DTPA-D-Phe1]octreotide scintigraphy scan demonstrated a positive image for somatostatin receptors in exactly the same location and surgery confirmed the presence of a small ACTH-secreting carcinoid tumour in the upper left lung lobe which was resected. Surgery cured the hypercorticism of the patient. The differential diagnosis of Cushing's syndrome and the procedure for localisation of an ACTH source are discussed.

Topics: ACTH Syndrome, Ectopic; Adult; Carcinoid Tumor; Humans; Indium Radioisotopes; Lung Neoplasms; Male; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals

A wide variety of neuroendocrine tumours express somatostatin receptors, and can be visualized by radiolabelled somatostatin analogue scintigraphy. To investigate the value of [111In]-octreotide scintigraphy (Octreoscan), 48 patients (37 with proven carcinoid, pancreatic endocrine and medullary carcinoma of thyroid tumours, 11 with neuroendocrine syndromes multiple endocrine neoplasia (MEN-I) and Zollinger-Ellison syndrome (ZES) were examined with 111In-DTPA-D-Phe1-octreotide. Scintigrams were obtained at 24 and 48 h, and the results were compared with CT and magnetic resonance imaging (MRI). Thirty-five of 48 patients had positive [111In]-octreotide scintigraphy (23/25 (92%) carcinoids, 8/9 (89%) PETs, 4/11 (36%) MEN-I & ZES). Of the 42 lesions located by conventional imaging techniques, 37 (88%) were also identified by Octreoscan. Unexpected lesions (40 sites), not detected by CT or MR imaging were found in 24/48 (50%) patients. [111In]-octreotide scintigraphy has a higher sensitivity for tumour detection, and is superior to MR imaging and CT scanning in the identification of previously unsuspected extraliver and lymph node metastases. It may also be helpful for the localization of clinically suspected tumours in patients with MEN-I and ZES.

Topics: Adolescent; Adult; Aged; Carcinoid Tumor; Carcinoma, Medullary; Child; Female; Humans; Indium Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Thyroid Neoplasms; Tomography, X-Ray Computed

Radiolabeled somatostatin analogs have shown uptake in a variety of tumors. These include carcinoid, Merkel cell carcinoma, pheochromocytoma, islet cell tumor, and other tumors with somatostatin receptors. Radiolabeled somatostatin analog imaging with Indium-111-DTPA-pentetreotide permits whole body imaging, providing a new safe and effective means for detection of primary tumors and metastatic foci in neoplasms with somatostatin receptors. This imaging modality is helpful in screening the entire body as well as evaluating questionable foci of disease identified by conventional imaging modalities. This case report demonstrates the utility of computed tomography (CT) and radiolabeled somatostatin imaging as complementary modalities in the workup of a patient with metastatic carcinoid tumor.

Topics: Aged; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Intestinal Neoplasms; Intestine, Small; Liver Neoplasms; Malignant Carcinoid Syndrome; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Tomography, X-Ray Computed

This report describes a technique that increases the specificity of 111In-pentetreotide as evaluated in a patient with ectopic Cushing syndrome.. Two separate SPECT studies were performed with different pharmacologic protocols, both including treatment with cold octreotide. The imaging protocol provides acquisitions at 4 and 24 hr after injection. The quantitative approach was based on the ROI activity (manually designed) of an area of pathological lung uptake (ROI-T) versus background (ROI-NT). Histological, histochemical and specific mRNA measurements confirmed the presence of an SSR2 receptor carcinoid in the lung.. The time course of ROI-T/ROI-NT is a linear increase between 4 and 24 hr. Washout with cold octreotide diminished the ROI-T activity content and the saturation protocol increased ROI-T/ROI-NT, confirming the specific nature of the uptake.. Displacement and saturation protocols in 111In-pentetreotide imaging demonstrated the specificity of tumor binding.

Topics: ACTH Syndrome, Ectopic; Adult; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Lung Neoplasms; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Time Factors; Tomography, Emission-Computed, Single-Photon

We report a case of a hepatic carcinoid metastasis mimicking a hemangioma on ultrasound and on CT. Indium-111-DTPA-D-Phe-1-octreotide (111In-OCT) and 123I-vasoactive intestinal peptide (123I-VIP) receptor images suggested a carcinoid metastasis of the liver. The final diagnosis was established histopathologically. The differential diagnosis of liver lesions is discussed.

Topics: Carcinoid Tumor; Diagnosis, Differential; Female; Hemangioma; Humans; Indium Radioisotopes; Iodine Radioisotopes; Liver Neoplasms; Middle Aged; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Receptors, Vasoactive Intestinal Peptide; Tomography, Emission-Computed, Single-Photon

Bronchial carcinoid tumors are neuroendocrine neoplasms capable of expressing somatostatin receptors and of secreting neuromediators such as ACTH and chromogranins. Radiologic appearance is usually non-specific and has to be distinguished from benign pulmonary nodules and other malignant diseases. Standard radiological techniques have limited accuracy in the evaluation of such lesions. Radioisotopic imaging techniques may increase the specificity of diagnostic assessment. The role of immunoscintigraphy with anti-chromogranin A and B monoclonal antibodies (MoAbs) and of 111In-Octreoscan scintigraphy is evaluated in two cases of bronchial carcinoid tumors associated to Cushing syndrome.

Topics: Adolescent; Bronchial Neoplasms; Carcinoid Tumor; Chromogranin A; Chromogranins; Cushing Syndrome; Female; Humans; Indium Radioisotopes; Male; Octreotide; Pentetic Acid; Radioimmunodetection; Radiopharmaceuticals

Somatostatin receptor scintigraphy is used to diagnose carcinoid of the gastrointestinal tract. Its sensitivity ranges from approximately 75%-100%. Therefore, it was hypothesized that it can be used in the postsurgical follow-up to detect residual carcinoid, recurrence, and metastatic disease.. This article is concerned with the findings of somatostatin receptor imaging performed on a 12-year-old girl 8 weeks after appendectomy. Histologic examination showed an incidental appendix carcinoid. Somatostatin receptor scintigraphy performed for detection of lymph node metastatic spread of the carcinoid showed focal tracer accumulation at the former operative site; subsequently, a right hemicolectomy was performed. However, histologic examination of the surgical tissue showed no evidence for carcinoid.. It is concluded that there are some potential pitfalls for somatostatin receptor imaging at least soon after surgery. Therefore, it should not be used to aid in reoperation.

Topics: Appendiceal Neoplasms; Carcinoid Tumor; Child; Female; Humans; Indium Radioisotopes; Lymphatic Metastasis; Neoplasm, Residual; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin

Superimposition of SPECT and computed tomography (CT) slices from the thoracoabdominal region was achieved without the use of external markers for 14 studies in 13 patients with endocrine carcinoma. Technical feasibility and clinical validation of this retrospective fusion method were assessed.. Patients had a history of thyroid cancer or of carcinoid tumor. To detect tumor sites, CT scan and dual-isotope tomoscintigraphy were performed, with 99mTc-hydroxymethylene diphosphonate for bone scintigraphy and with 111In-pentetreotide, 131I or 131I-metaiodobenzylguanidine for tumor scintigraphy (TS). A superimposition method previously developed for the pelvic region was adapted to the nonrigid thoraco-abdominal region. CT-bone scintigraphy and CT-TS superimposed images were obtained. Clinical validation of the information obtained from the superimposed images was obtained from surgery or follow-up imaging studies performed after clinical evolution of the disease process.. Reliable and reproducible registration was achieved in all patients. CT-TS superimposed images produced accurate localization of abnormal TS foci. Accuracy was limited primarily by variable relative displacements of the thoracoabdominal organs. For 10 sites in 8 patients, localization and/or characterization obtained from CT-TS images was confirmed by a reference technique. Superimposition enabled the localization of tumor sites that otherwise could not have been suspected from CT alone and allowed the characterization of CT suspicious masses and the confirmation of CT positive sites. Nonspecific tumor TS uptake sites were also localized.. With standard CT and dual-isotope SPECT acquisitions, SPECT-CT fusion is feasible in the thoracoabdominal region without the use of external markers. Fused images were validated in 8 patients for 10 sites. The use of this technique could probably improve the management and care of patients with endocrine carcinoma.

Topics: 3-Iodobenzylguanidine; Abdominal Neoplasms; Carcinoid Tumor; Carcinoma, Medullary; Feasibility Studies; Humans; Image Processing, Computer-Assisted; Indium Radioisotopes; Iodine Radioisotopes; Iodobenzenes; Octreotide; Pentetic Acid; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Technetium Tc 99m Medronate; Thoracic Neoplasms; Thyroid Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Sixty-four consecutive patients with disseminated midgut carcinoids were treated during an 8-year period according to a single clinical protocol aimed at aggressive tumor reduction by surgery alone or with subsequent hepatic artery embolization. All patients had markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels (581 +/- 79 micromol/24 h) and hormonal symptoms. Fourteen patients (22%) reached anatomic and biochemical cure by surgery alone. At follow-up, the mean 5-HIAA levels were still normal after 69.0 +/- 6. 2 months; two patients had died from unrelated causes. With the introduction of somatostatin receptor scintigraphy, subclinical disease was diagnosed in 7 of these 14 patients. Forty patients with bilobar hepatic disease underwent embolization in combination with octreotide. In this group, 5-HIAA levels were still reduced by 55% after 71 +/- 11 months of follow-up, and the 5-year survival was 56%, estimated from the total death hazard function. After embolization, two subgroups could be identified with marked differences in their long-term response to treatment. Ten patients were not embolized owing to complicating diseases. The 5-year survival for the entire series was 58%. A significantly increased risk of cardiovascular deaths was seen, which underlines the importance of total survival analysis in a disease with multiple hormonal effects. It is concluded that an active surgical approach must be recommended to patients with the midgut carcinoid syndrome. In patients with bilobar hepatic disease, embolization combined with octreotide treatment markedly reduced the 5-HIAA excretion and suggested a prolonged 5-year survival.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Carcinoid Tumor; Cause of Death; Clinical Protocols; Combined Modality Therapy; Death, Sudden, Cardiac; Embolization, Therapeutic; Female; Follow-Up Studies; Hepatic Artery; Humans; Hydroxyindoleacetic Acid; Indium Radioisotopes; Intestinal Neoplasms; Liver Neoplasms; Male; Middle Aged; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; Remission Induction; Risk Factors; Survival Analysis; Survival Rate

We analyzed the results of conventional imaging and somatostatin receptor scintigraphy in 150 patients with neuroendocrine tumors.. The outcomes of combinations of imaging modalities were compared in terms of tumor localization, effect on patient management and financial costs.. In patients with carcinoids, a combination of somatostatin receptor scintigraphy, chest radiograph and ultrasound of the upper abdomen had a high sensitivity for tumor localization, and detected lesions in patients in whom no tumor was found with conventional imaging, justifying the greater cost. In patients with medullary thyroid carcinoma, somatostatin receptor scintigraphy adds little to the information obtained with conventional imaging and therefore should not be used as a screening method. In patients with paraganglioma, CT scanning of the region where a paraganglioma is suspected, followed by somatostatin receptor scintigraphy to detect multicentricity has the best cost effectiveness ratio. In patients with gastrinomas, the combination of somatostatin receptor scintigraphy and CT scanning of the upper abdomen had the highest sensitivity. The relatively high cost of this process is outweighed by its demonstrating a resectable tumor. In patients with insulinomas, the highest yield against the lowest cost is obtained if somatostatin receptor scintigraphy is only performed if CT scanning fails to demonstrate the tumor.. Somatostatin receptor scintigraphy should be performed in patients with small-cell lung carcinoma because it can lead to a change of stage and may demonstrate otherwise undetected brain metastases. The cost increase is outweighed by the omission of unnecessary treatment for some of the patients and by the possibility of irradiating brain metastases at an early stage, which may lead to a better quality of life.

Topics: Carcinoid Tumor; Carcinoma, Medullary; Carcinoma, Small Cell; Cost-Benefit Analysis; Costs and Cost Analysis; Humans; Indium Radioisotopes; Lung Neoplasms; Netherlands; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Paraganglioma; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity; Thyroid Neoplasms; Tomography, X-Ray Computed

Topics: Adult; Carcinoid Tumor; Humans; Indium Radioisotopes; Male; Multiple Endocrine Neoplasia Type 1; Octreotide; Pentetic Acid; Radionuclide Imaging; Thymus Neoplasms

Scintigraphy with long-acting somatostatin (SST) analogues may be useful for the localization of tumours expressing receptors (R) for SST. In this study we have analysed the in vitro and in vivo binding properties of three SST analogues, 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. In vitro binding studies performed with a variety of primary tumours (n=48) as well as with several tumour cell lines (A431, HT29, PANC1, COLO320, HMC1, KU812) indicated significant in vitro binding of these three radiolabelled SST analogues to two subpopulations of SSTR, high (Kd 0.2-2.0 nM) and low (Kd 5-15 nM) affinity ones. The number of SSTR on tumour cells was at least a 1000-fold higher as compared with normal peripheral blood cells. Comparative scintigraphic studies using 123I-OCT and/or 123I-Tyr-3-OCT and/or 111In-DTPA-d-Phe-1-OCT were performed in 21 patients with histologically verified intestinal carcinoid tumours. Corresponding scintigraphic results were obtained in 18 of 21 patients investigated with two different SSTR ligands, either 123I-OCT/123I-Tyr-3-OCT (four of five), 123I-OCT/111In-DTPA-d-Phe-1-OCT (eight of nine), or 123I-Tyr-3-OCT/111In-DTPA-d-Phe-1-OCT (six of seven). We conclude that various tumours express high amounts of SSTR which are recognized by three radiolabelled SST analogues: 123I-OCT, 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. Differences between these SST analogues in their in vitro binding and/or in vivo scanning properties are observed in a minority of patients. Thus, the labelling of OCT with iodine may be an alternative approach for those nuclear medicine departments for which 111In-DTPA-d-Phe-1-OCT is not easily available, or is too expensive.

Topics: Adolescent; Adult; Aged; Carcinoid Tumor; Female; Humans; In Vitro Techniques; Indium Radioisotopes; Iodine Radioisotopes; Male; Middle Aged; Neoplasms; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Tumor Cells, Cultured

Compared with other imaging modalities and clinical investigation, the 111In-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean (+/- SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% (+/- 6%). 8 patients had < 50% and 10 had > 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discussed.

Topics: Carcinoid Tumor; Female; Hormone Antagonists; Humans; Hydroxyindoleacetic Acid; Indium Radioisotopes; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin; Survival Analysis

We evaluated a hand-held scintillation detector for intra-operative localisation of somatostatin-receptor-positive tumours in situ, and after excision, as an addition to preoperative scintigraphy with [111In-DTPA-Phe1]octreotide. Using the hand-held detector, the suspect tumour/normal tissue ratio R(in situ) between measurements was calculated for 23 patients with neuroendocrine tumours. The count rates of excised tumour and normal tissue were also measured ex vivo and their ratio R(ex vivo) was calculated. In midgut carcinoid (MC) patients (all scintigraphy positive), 4/29 macroscopically identified tumours gave false R(in situ). Tumour/blood 111In activity (T/B) ratios measured in a gamma counter were all high (27-650). In patients with medullary thyroid carcinoma (8/10 scintigraphy positive), misleading R(in situ) were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in MC patients. 2/4 patients with endocrine pancreatic tumours (EPTs) had positive scintigraphy, reliable intra-operative measurements, and very high T/B ratios (910-1,500). 1 patient with a gastric carcinoid had correct R(in situ) and R(ex vivo), with high T/B ratios (71-210). 1 patient with sporadic insulinoma had negative scintigraphy and 1 patient with neuroendocrine carcinoma of the uterus also had low T/B ratios. In most cases, in situ measurements added little information to preoperative scintigraphy and surgical findings. The very high T/B ratios seen in MC tumours and some EPTs seem promising for future radiotherapy via somatostatin receptors.

Topics: Carcinoid Tumor; Carcinoma, Medullary; Humans; Indium Radioisotopes; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging

Topics: ACTH Syndrome, Ectopic; Adult; Bronchial Neoplasms; Carcinoid Tumor; Humans; Indium Radioisotopes; Male; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals

Neuroendocrine tumor cells frequently overexpress somatostatin receptors at their cell surfaces. To evaluate the possibility of using the somatostatin analog 111In-DTPA-D-Phe1-octreotide for radiation therapy, we studied the binding and subsequent internalization of 111In into three types of cultured human neuroendocrine tumor cells.. Primary cultures of gastric carcinoid, midgut carcinoid and glucagonoma cells were incubated with 111In-DTPA-D-Phe1-octreotide and cell-surface bound, internalized and released 111In activity was measured. Electron microscopic autoradiography was also performed.. All three cell types specifically (80%-95%) bound 111In-DTPA-D-Phe1-octreotide and internalized 111In. After 1 hr pulse incubation with 111In-DTPA-D-Phe1-octreotide, there was an initial decrease in intracellular 111In to about 50% during the subsequent 6-hr incubation. Almost no further release was observed during the remaining 18-42 hr studied. Autoradiography showed that the internalized 111In was found in the cytoplasm and nucleus in the midgut carcinoid cells.. Indium-111 DTPA-D-Phe1-octreotide might be useful for radiation therapy of patients with surgically incurable tumors having high somatostatin receptor densities.

Topics: Autoradiography; Carcinoid Tumor; Gastrointestinal Neoplasms; Glucagonoma; Humans; Indium Radioisotopes; Octreotide; Pentetic Acid; Radionuclide Imaging; Tumor Cells, Cultured

We have performed 100 scintigraphic investigations using [111In-diethylenetriaminepentaacetic acid-D-Phe1]octreotide (111In-octreotide) single photon emission tomography (SPECT) in patients with carcinoid tumors. One or several lesions could be detected in 77 cases, and true negative results were obtained in 11 cases. There were false-negative results in 12 cases compared with results from conventional radiological methods. The ratio between the SPECT signals from the area with the highest uptake and normal lung was used as a tumor:background ratio. An attenuation correction was made in all investigations. We found that lesions in untreated patients had lower tumor:background ratios compared with those in patients treated with somatostatin analogues (medians, 10 and 40, respectively; P < 0.001) or IFN (median, 23; P = 0.03). In untreated patients, there was a correlation between the tumor:background ratio and the levels of urinary 5-hydroxyindoleacetic acid (U-5HIAA) and p-chromogranin A. The data obtained in the present investigation indicate that somatostatin receptor expression might be influenced by the treatment; i.e., a higher tumor:background ratio is found in patients treated with either somatostatin analogues or IFN. Furthermore, it was found that somatostatin receptor expression correlates with the levels of U-5HIAA and p-chromogranin A in untreated patients, and that 111In-octreotide SPECT scintigraphy is more likely positive in patients with elevated U-5HIAA values. This indicates that somatostatin receptor expression and elevated U-5HIAA are more likely present in patients with highly differentiated tumors and, thus, could be of prognostic value.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Intestinal Neoplasms; Male; Middle Aged; Octreotide; Pentetic Acid; Radioligand Assay; Receptors, Somatostatin; Tomography, Emission-Computed, Single-Photon

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

Topics: Adult; Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoid Tumor; Carcinoma, Medullary; False Positive Reactions; Female; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Iodine Radioisotopes; Liver Neoplasms; Male; Middle Aged; Octreotide; Organotechnetium Compounds; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms

Indium-111 activity concentrations in human tumor and normal tissue samples were determined at 24, 48 and 120 hr after i.v. injection of 111In-DTPA-D-Phe-1-octreotide. Fourteen patients were included in the study. Seven patients had medullary thyroid carcinoma, four had midgut carcinoid tumors, two had endocrine pancreatic tumors and one had chronic pancreatitis.. For midgut carcinoids, the tumor-to-blood ratio was 51:220, for medullary thyroid carcinoma 4:39, and for two endocrine pancreatic tumors 6 and 1500. Tumor-to-muscle ratios varied between 1 and 1200 and tumor-to-fat between 2 and 1500 depending on tumor type.. The sometimes extremely high tumor-to-normal tissue ratios present the possibility for use of radiolabeled octreotide for radiation therapy of somatostatin receptor positive tumors.

Topics: Abdominal Neoplasms; Adult; Aged; Carcinoid Tumor; Chronic Disease; Female; Humans; Indium Radioisotopes; Injections, Intravenous; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Pancreatitis; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Reference Values; Thyroid Neoplasms

Scintigraphy with radiolabelled analogue of somatostatin is highly sensitive in detecting carcinoid tumors especially if performed with Single Photon Computed Tomography (SPECT). In this report we describe our experience with 111In-DTPA-Octreotide in a female patient affected by a small asymptomatic intrabronchial carcinoid demonstrated by CT scan and bronchial endoscopy performed after recurrent left pneumonias. Planar views and SPECT images, using 111In-DTPA-Octreotide, were collected before and four hours after the first endoscopic laser resection. All groups of SPECT images were positive in the left parahilar region but at a different degree. Scans performed after resection showed a low degree of uptake which was considered to be probably secondary to local swelling; CT scan was negative. Follow up endoscopic biopsy repeated at six months, showed a relapse always in the same site; CT scan of the thorax was again negative. 111In-DTPA-Octreotide images obtained at twelve months were positive always in the left parahilar region, CT scan was negative but another biopsy was not possible. Therefore it was suspected a relapse of the carcinoid which was probably growing only through the bronchial wall without spreading towards the bronchial lumen and/or the lung parenchima. In this occasion, it was also thought that images collected four hours after resection could be positive not only for swelling but for a relapse as well. In every scintigraphic session, SPECT images presented higher quality than planar. This case suggests that 111In-DTPA-Octreotide SPECT is a non-invasive diagnostic technique which could be applied as a follow-up tool especially to patients with no-secreting carcinoid neoplasm and/or with negative or doubtful endoscopic and radiological investigations.

Topics: Adult; Bronchial Neoplasms; Carcinoid Tumor; Female; Humans; Octreotide; Pentetic Acid; Tomography, Emission-Computed, Single-Photon

High numbers of high-affinity somatostatin binding sites have been found on carcinoid tumors, gastrinomas, small cell lung cancers and the majority of medullary thyroid cancers, enabling in vivo visualization of these tumors with octreotide scintigraphy. A comparison of the results obtained at our institution and another 15 centers in Europe show a few remarkable similarities and differences. The overall sensitivity of octreotide receptor scintigraphy to detect the primary GEP tumor and its metastases is high, e.g. 80-90%. The main difference was found in gastrinomas and to a lesser extent in insulinomas. These differences might be attributed to different scanning protocols. Furthermore, octreotide scintigraphy also has a high sensitivity to localize the primary tumor and its metastases causing Cushing's syndrome by ectopic production of ACTH or CRH. Octreotide scintigraphy is a new, sensitive and noninvasive technique to localize somatostatin receptor expressing endocrine tumors and their metastases.

Topics: Carcinoid Tumor; Cushing Syndrome; Gastrinoma; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Lung Neoplasms; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Receptors, Somatostatin; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

This study was performed to evaluate whether the presence or absence of somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D-Phe1]octreotide scintigraphy can be used to predict response to somatostatin analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid tumours and two with foregut carcinoid tumours. Twenty-seven patients showed pathological uptake in tumour lesions at scintigraphy; of these, 22 responded to somatostatin analogue treatment using octreotide, somatuline or octastatin, while five patients failed to respond. None of the three patients displaying negative scintigraphic investigations responded to treatment with somatostatin analogues. These results show a good correlation between the somatostatin receptor status and the patients' ability to respond to somatostatin analogue treatment (p = 0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]octreotide can be used to select patients with malignant carcinoid tumours suitable for somatostatin analogue treatment and exclude those that will not benefit from such medication.

Topics: Aged; Carcinoid Tumor; Female; Forecasting; Humans; Indium Radioisotopes; Intestinal Neoplasms; Male; Middle Aged; Octreotide; Pentetic Acid; Peptides, Cyclic; Prospective Studies; Radionuclide Imaging; Retrospective Studies; Somatostatin; Tomography, X-Ray Computed; Treatment Outcome

To determine the value of somatostatin-receptor scintigraphy in the localization of various endocrine gastrointestinal tumors, we compared the results obtained with this new technique with the results obtained with computed tomography and sonography. We could not find an overall advantage of somatostatin-receptor scintigraphy as compared to computed tomography or sonography in the localization of intestinal carcinoids (n = 13), gastrinomas (n = 12), functionally non-active endocrine pancreatic tumors (n = 8) and various other endocrine pancreatic tumors (n = 4). In 2 patients with endocrine pancreatic tumors however, the tumors were localized preoperatively only by somatostatin-receptor scintigraphy. Somatostatin-receptor scintigraphy may occasionally be helpful in the localization of gastrointestinal endocrine tumors if these tumors are not localized by conventional imaging studies. Somatostatin-receptor scintigraphy does not solve the problem to localize small endocrine tumors.

Topics: Biomarkers, Tumor; Carcinoid Tumor; Gastrinoma; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Insulinoma; Multiple Endocrine Neoplasia Type 1; Octreotide; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pentetic Acid; Receptors, Somatostatin; Tomography, Emission-Computed, Single-Photon; Zollinger-Ellison Syndrome

111In-diethylenetriamine penta-acetate-D-Phe1-octreotide scintigraphy was evaluated in a group of 27 patients with disseminated midgut carcinoid tumour. Additional information gained by the intraoperative use of a scintillation detector was studied in five patients with midgut carcinoid tumours and in two with endocrine pancreatic tumours. In 19 patients tumours not recognized by non-invasive radiological methods were visualized in 27 locations, most commonly in liver and para-aortic lymph nodes. Three false-negative tumour locations were noted (ovarian and peritoneal). With guidance from scintigraphic findings, nine patients underwent surgical tumour reduction, leading to complete remission in three. Clinically suspect tumour lesions were measured by the detector in situ, and ex vivo after excision. After excision the tissue:blood activity concentration ratios were calculated. In situ measurements were helpful in the localization of tumours and in the control of adequate clearance of tumour tissue. High tissue:blood activity concentration ratios at 1, 2 and 5 days in the five patients with midgut carcinoid tumour indicate a potential role for radiation therapy with radiolabelled octreotide in patients with somatostatin receptor-positive tumours.

Topics: Carcinoid Tumor; Humans; Intraoperative Care; Octreotide; Pentetic Acid; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Topics: Adult; Aged; Carcinoid Tumor; Female; Follow-Up Studies; Gamma Cameras; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Intraoperative Care; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Pentetic Acid; Postoperative Care; Preoperative Care; Radiology, Interventional; Receptors, Somatostatin; Tomography, Emission-Computed, Single-Photon

Topics: Carcinoid Tumor; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity

Somatostatin-receptor scintigraphy using the 111In-labelled somatostatin-analogue octreotide ([111In-DTPA-D-Phe1]-octreotide) was performed in 40 patients with carcinoid tumours. In 31/40 patients, this scintigraphy proved positive compared with the 33/40 patients whose tumours were disclosed on CT scans. In addition, 18 previously unidentified lesions were detected with this scintigraphy. Two of these lesions represented previously undetectable primary tumours. It is concluded that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide has a future role in the staging of patients with carcinoid disease.

Topics: Adult; Aged; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Male; Middle Aged; Octreotide; Pentetic Acid; Receptors, Somatostatin; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Receptor scintigraphy with 111In-pentetreotide is a simple method with a sensitivity of 86% for the localization of the primary tumor and its metastases in patients presenting with the clinical and biochemical symptoms of an endocrine tumor of the gastrointestinal tract or the pancreas. As a whole-body scintigraphic technique it covers all body regions and is also able to reveal small tumors which either cannot be detected or can only be detected with difficulty by the usual imaging methods. In 85 patients with GEP tumors or after operative removal of such tumors, receptor scintigraphy proved to be superior to ultrasound and computed tomography in 34%, equal in 52%, and inferior in 14% of the cases.

Topics: Aged; Carcinoid Tumor; Gastrinoma; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Insulinoma; Metabolic Clearance Rate; Neoplasm Metastasis; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Tissue Distribution

The distribution and elimination characteristics of the 111In-labelled somatostatin analogue OctreoScan111 were studied in 23 patients with malignant tumours. The substance exhibited a rapid blood elimination following a bi-phasic pattern. The initial part of the elimination curves showed a t1/2a of between 0.27 and 3.6 h. The patients investigated had creatinine clearance rates ranging from 33 to 124 ml/min. However, within this range, no apparent correlation was found between the OctreoScan111 elimination rate and kidney function. Also no correlation was observed between the amount of administered activity and the elimination rate of OctreoScan111. The serum radioactivity of 6 patients was analyzed with respect to molecular size. These experiments showed that OctreoScan111 circulated unbound in serum. About 3% of the radioactivity, most probably representing 111In-chloride of DTPA-111In-chloride, circulated protein-bound. The elimination of OctreoScan111 radioactivity in urine displayed a bi-phasic pattern. Size separation of the radioactivity appearing in the urine after 24 h showed a higher molecular weight when compared with OctreoScan111, indicating the existence of a metabolite of the injected substance. The results obtained are discussed in the light of a potential role for the substance in systemic radiotherapy.

Topics: Adenoma, Islet Cell; Adult; Aged; Carcinoid Tumor; Chromatography, Gel; Endocrine Gland Neoplasms; Female; Half-Life; Humans; Indium Radioisotopes; Kidney; Male; Middle Aged; Molecular Weight; Neoplasms; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Thyroid Neoplasms

Scintigraphy with a radiolabelled somatostatin analog represents a new highly specific approach in the diagnostic work-up of receptor-positive APUD tumours and their metastases. We present our preliminary results with somatostatin receptor scintigraphy in 15 patients with histologically proven midgut carcinoid. 5 out of 6 primary tumour sites (83%) and 90% of the known metastatic lesions could be detected; unknown metastatic lesions were seen in 5 patients. Compared with other nuclear medicine procedures somatostatin receptor scintigraphy is able to detect all tumour sites within hours. This advantage will promote the acceptance of this sensitive and specific imaging modality by the clinicians with regard to preoperative work-up and symptomatic therapy with a somatostatin analog.

Topics: Adult; Aged; Carcinoid Tumor; Female; Humans; Indium Radioisotopes; Intestinal Neoplasms; Intestine, Small; Liver Neoplasms; Male; Methods; Middle Aged; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatotropin; Time Factors