(dtpa-phe(1))-octreotide and Carcinoma--Medullary

Current therapeutic approaches in neuroendocrine tumours include surgery, radiotherapy and polychemotherapy. Different metabolic patterns of neuroendocrine tumours allow the use of a wide range of diagnostic options in nuclear medicine, due to the presence of a wide spectrum of radiotracers electively concentrating in these neoplasms. Nuclear medicine, and in particular 111In Octreotide (OCT) scintigraphy, 123I Methaiodobenzylguanidine (MIBG) and pentavalent 99mTc-DMSA (V-DMSA), together with biohumoral markers, are currently able to locate tumours also not detectable using traditional diagnostic techniques. Somatostatin analogs, such as octreotide have become increasingly important over the years in the treatment of patients with neuroendocrine tumours. At present the therapeutic use of somatostatin analogs can be schematised as 1) pharmacological treatment (with cold octreotide); 2) surgical treatment (radioguided surgery); 3) radiometabolic treatment (with marked octreotide). The development of new synthetic molecules and new radiocompounds will probably open up interesting scenarios in the near future.

Topics: Adrenal Gland Neoplasms; Adrenalectomy; Antineoplastic Agents, Hormonal; Carcinoma, Medullary; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Humans; Indium Radioisotopes; Lung Neoplasms; Neoplasm Proteins; Neuroendocrine Tumors; Octreotide; Pentetic Acid; Pheochromocytoma; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Surgery, Computer-Assisted; Thyroid Neoplasms; Thyroidectomy; Tomography, X-Ray Computed

Although serum calcitonin and CEA are sensitive indicators for the presence of medullary thyroid carcinoma (MTC), the localization of tumor sites may be very difficult. In an approach to localize MTC lesions we performed comparative in vivo studies in 12 patients with primary MTC and in 4 patients with suspected recurrent MTC using 123I-VIP (150 MBq/1 microgram) and 111In-DTPA-D-Phe-1-octreotide (111In-OCT; 150 MBq/1 microgram). Despite elevated calcitonin values in all patients with suspected recurrent or metastatic lesions, both ultrasound and computed tomography (CT) were unable to localize a tumor site. 111In-OCT localized the primary tumor in the thyroid gland in 7 of 11 patients (63.5%). In 2 of 4 patients (50%) with suspected recurrent MTC, pathological uptake of 111In-OCT in the mediastinum or liver was demonstrable. In none of the 11 patients did 123I-VIP-receptor scanning indicate primary, recurrent, or metastatic tumor lesions. In vitro binding studies showed an absence of high-affinity VIP receptors in MTC tissue, whereas high-affinity 111In-OCT receptors were present in 4 of 6, and low-affinity 123I-VIP as well as 111In-OCT receptors were present in 6 of 6 MTC tissue samples. We conclude that somatostatin receptor scanning using 111In-OCT may visualize primary MTC, but it has only a low sensitivity in the detection of recurrent disease. The 123I-VIP-receptor scan is not helpful in the localization diagnosis of primary or recurrent MTC.

Topics: Adult; Aged; Carcinoma, Medullary; Female; Humans; Indium Radioisotopes; Iodine Radioisotopes; Male; Middle Aged; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

Somatostatin receptor-positive lesions can be visualized by scintigraphy using [111In-DTPA0]octreotide. Recently, there have been reports of differences in receptor binding between somatostatin receptor subtypes and between somatostatin analogues, such as RC-160 and octreotide, as well as of differences in internalization between the somatostatin receptor subtypes. The possibility that certain somatostatin receptor-positive tissues and tumours which do not bind octreotide may bind and internalize RC-160 would open new scintigraphic or radiotherapeutic applications of radiolabelled RC-160. We investigated the metabolism and tissue distribution of [111In-DTPA0]RC-160 in comparison with [111In-DTPA0]octreotide in four patients after injection of 250 MBq (10 microgram) of these radiopharmaceuticals. Patient 1 had a metastatic follicular thyroid carcinoma, patient 2 a metastatic medullary thyroid carcinoma, patient 3 tuberculosis and patient 4 an insulinoma. The plasma clearance of the [111In-DTPA0]RC-160 was slower than that of [111In-DTPA0]octreotide, with 5% and 2%, respectively, of the initial plasma radioactivity remaining at 10 h p.i. The urinary excretion of [111In-DTPA0]RC-160 was initially also slower than that of [111In-DTPA0]octreotide, but the cumulative excretion of radioactivity was not significantly different at 48 h p.i. Approximately 80% of injected radioactivity was cleared in the urine, while in one patient 20% of the injected dose was recovered in the faeces. The slower clearance of [111In-DTPA0]RC-160 resulted in a higher background in all organs studied i.e. liver, spleen, kidneys and lungs, at 24 h p.i. Although the target to background ratio with [111In-DTPA0]octreotide was higher, no differences were found between the two analogues with regard to their sensitivity in detecting lesions in these four patients. We conclude that although only four subjects were studied, [111In-DTPA0]RC-160 does not appear to have additional value for scintigraphy and is associated with higher background activity.

Topics: Adenocarcinoma, Follicular; Adult; Carcinoma, Medullary; Female; Humans; Indium Radioisotopes; Insulinoma; Male; Middle Aged; Octreotide; Oligopeptides; Organ Specificity; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Thyroid Neoplasms; Tuberculosis

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

The early detection of all tumor sites in patients with medullary thyroid carcinoma (MTC) before primary surgery is important, because MTC tends to metastasize to regional lymph nodes of the neck and mediastinum early during the course of the disease.. In an approach to localize the primary tumor sites and to detect additional tumor involvement, we have performed in 22 patients with MTC either 99mTc(V)-dimercaptosuccinic acid (DMSA) and/or 111In-diethylenetriamine pentaacetic acid-D-Phe-1-octreotide scintigraphy.. Indium-111-octreotide (150-200 MBq) identified the primary tumor in 10 of 14 patients (71%), whereas the primary tumor was visualized by 99mTc-DMSA (300-370 MBq) in 10 of 17 patients (58%). In 8 of 22 patients (36%), lymph node metastases were present at the time of diagnosis, as confirmed by histopathology and histochemistry after surgery (all <2 mm). Preoperatively, neither scan was able to detect lymph node involvement in these patients (0/8).. Both 99mTc-DMSA and 111In-octreotide studies have similar sensitivity to localize primary MTC; however, these scans are not able to detect small lymph node involvement (micrometastases) before initial surgery. Unfortunately, both scans have no clinical implication for preoperative staging in patients with MTC.

Topics: Carcinoma, Medullary; Female; Humans; Indium Radioisotopes; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Octreotide; Pentetic Acid; Preoperative Care; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms

Topics: Carcinoma, Medullary; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Indium Radioisotopes; Meningioma; Middle Aged; Neoplasm Recurrence, Local; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Thyroid Neoplasms

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

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

We evaluated the clinical utility of positive somatostatin receptor scintigraphy in patients with medullary thyroid cancer (MTC).. Twenty-four MTC patients with increased calcitonin levels underwent somatostatin receptor scintigraphy using 111In-pentetreotide (120-200 MBq) with early (4 hr after injection) and delayed (24 hr) whole-body scans and liver SPECT imaging. In Group 1 (12 patients), conventional imaging modalities demonstrated the presence of tumor sites prior to somatostatin receptor scintigraphy; in Group 2 (12 patients), conventional imaging modalities were negative or inconclusive.. Somatostatin receptor scintigraphy had positive results in 9 of 24 patients (37%): of Group 1 patients, 7 of 12 had positive somatostatin receptor scintigraphy results. Of these patients cases, somatostatin receptor scintigraphy demonstrated several involved organs and tumor sites either identical (two patients) or smaller (five patients) in size than conventional imaging modalities. Only two patients in Group 2 had positive somatostatin receptor scintigraphy results which demonstrated significant mediastinal uptake previously classified as indeterminate on conventional imaging modalities. No new tumor site was identified nor were therapeutic options modified by the somatostatin receptor scintigraphy results.. Somatostatin receptor scintigraphy only demonstrates part of tumor sites and cannot visualize small tumor sites (< or = 1 cm). We believe that somatostatin receptor scintigraphy has a limited role in the management of MTC patients.

Topics: Adult; Aged; Carcinoma, Medullary; Female; Humans; Indium Radioisotopes; Liver Neoplasms; Male; Middle Aged; Octreotide; Pentetic Acid; Prospective Studies; Receptors, Somatostatin; Sensitivity and Specificity; Somatostatin; Thyroid Neoplasms; Tomography, Emission-Computed, Single-Photon

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

Detection of recurrence from medullary thyroid carcinoma (MTC) remains a diagnostic problem, especially when increased serum tumour marker levels suggest recurrence and conventional imaging techniques are non-diagnostic. In this study, we performed 111In-octreotide and 99mTc(V)-dimercaptosuccinic acid (DMSA) scans in a series of eleven patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole body studies detected tumour in six of the eleven patients studied and detected nine tumoral localizations. 99mTc(V)-DMSA whole body studies detected tumour in five of the eleven patients studied and eight tumoral localizations. 111In-octreotide and 99mTc(V)-DMSA studies detected recurrence in all four patients with basal calcitonin levels above 1000 ng/l. We conclude that 111In-octreotide and 99mTc(V)-DMSA studies have limited sensitivity to detect recurrence in patients with MTC, although their sensitivity may improve with high serum calcitonin levels. These radionuclide imaging techniques should be employed when conventional imaging techniques are negative or inconclusive or, in the case of 111In-octreotide studies, should be employed when we went to investigate the presence of somatostatin receptors that provide the basis for treatment with somatostatin analogues.

Topics: Adult; Biomarkers, Tumor; Calcitonin; Carcinoma, Medullary; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Octreotide; Organotechnetium Compounds; Pentetic Acid; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms

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

Topics: Adolescent; Adult; Aged; Calcitonin; Carcinoma, Medullary; Female; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Indium Radioisotopes; Male; Middle Aged; Neoplasm Recurrence, Local; Octreotide; Pentetic Acid; Receptors, Somatostatin; Thyroid Neoplasms; Tomography, Emission-Computed, Single-Photon