(dtpa-phe(1))-octreotide and Thyroid-Neoplasms

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

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

The medical approach to patients with secreting or clinically non-functioning pituitary adenoma as made considerable progress thanks to the use of new somatostatin analogs. They were first used to treat acromegaly in the mid 1980s and numerous studies have shown a reduction in GH concentration in over 90% of acromegalic patients. Good results were obtained using slow-release analog treatment also in TSH-secreting adenomas, whereas the therapeutic efficacy of these peptides in clinically non-functioning adenomas is still controversial. Treatment with somatostatin analogs improves symptoms, normalises hormone secretion and in some cases may induce a reduction in the volume of pituitary adenomas. Scintigraphy with octreotide may help to select patients who respond to this form of treatment.

Topics: Acromegaly; Adenoma; Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Antineoplastic Agents, Hormonal; Carcinoma; Humans; Indium Radioisotopes; Insulin-Like Growth Factor I; Kidney Neoplasms; Melanoma; Middle Aged; Octreotide; Pentetic Acid; Peptides, Cyclic; Pheochromocytoma; Pituitary Neoplasms; Predictive Value of Tests; Prolactinoma; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Somatostatin; Thymoma; Thymus Neoplasms; Thyroid Neoplasms; Thyrotropin; Treatment Outcome

111In-DTPA-octreotide is internalized by thyroid and neuroendocrine cancer cells via somatostatin receptor subtypes and can cause DNA damage by the emission of conversion and Auger electrons. The aim of the study was to determine the effect of 111In-DTPA-octreotide therapy in patients with progressive radioiodine non-responsive thyroid cancer in relation to 111In-DTPA-octreotide uptake by tumour localizations assessed on pre-treatment diagnostic octreotide scans.. Eleven consecutive patients, selected on positive pretreatment diagnostic scans, were treated with fixed doses of approx. 7400 MBq of 111In-DTPA-octreotide with an interval of 2-3 weeks between the doses. In one patient, the dose was adjusted because of sickle-cell disease. To assess the effects during treatment with 111In-DTPA-octreotide thyroglobulin levels were gathered from 2 years before treatment, during treatment and up to 1 year after treatment. A computed tomography scan was performed 3 months after the last treatment.. Two patients died during and shortly after the treatment course. Death was due to a sepsis and an insulin overdose, respectively. In 44% of the patients, stable disease was achieved up to 6 months after the first treatment according to both criteria. All four had relative low pretreatment thyroglobulin values (mean value 275 microg.l), representing limited metastasized disease. In two patients biochemical stable disease was observed, whereas computed tomography showed tumour progression.. Treatment with high doses of 111In-DTPA-octreotide in differentiated thyroid cancer results in a stable disease in a subgroup of patients. Our results suggest that a low pre-treatment thyroglobulin value, representing a small tumour load, may be a selection criterion for treatment.

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Iodine Radioisotopes; Male; Middle Aged; Octreotide; Patient Selection; Pentetic Acid; Pilot Projects; Prognosis; Radiopharmaceuticals; Thyroglobulin; Thyroid Neoplasms; Treatment Failure; Treatment Outcome

The utility of In-111 DTPA octreotide scintigraphy (SRS) for disease detection in patients with metastatic thyroid carcinoma (TCA) remains controversial. The authors compared the sensitivity of In-111-based SRS, F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and extensive conventional radiographic imaging (CRI) in this type of cancer.. SRS, FDG PET, and CRI were performed concurrently in 21 patients (age, 56.4 +/- 12.9 years) who had aggressive TCA. Concordance rates % of lesion positivity among pairs of different techniques (A and B) were calculated as the ratio of the number of lesions positive with both techniques divided by the sum of the total number of lesions positive with technique A + total number of lesions positive with technique B, which was then multiplied by 200.. The combined use of CRI, FDG PET, and SRS resulted in the detection of 105 lesions, presumed to be due to metastatic deposits. Sensitivities for SRS and FDG-PET imaging were 49.5% and 67.6%, respectively. The lesion detection concordance rates were as follows: CRI versus FDG PET, 80.8%; CRI versus SRS, 74.2%; and FDG-PET versus SRS, 58.6%. Importantly, SRS detected five unexpected lesions, which were negative by both CRI and FDG-PET imaging. In two representative patients, a positive correlation (Spearman's rank = 0.71; = 0.0576) existed between the percentage of lesional In-111 DTPA octreotide uptake and the standard uptake value in eight concordant lesions.. Although SRS has only moderate sensitivity for disease detection in metastatic TCA, sometimes it can reveal lesions that otherwise would be undetectable by either CRI or FDG-PET imaging.

Topics: Bone Neoplasms; Carcinoma; Cohort Studies; Female; Fluorodeoxyglucose F18; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinal Neoplasms; Middle Aged; Octreotide; Pentetic Acid; Pleural Neoplasms; Radiography; Radiopharmaceuticals; Sensitivity and Specificity; Skin Neoplasms; Thyroid Neoplasms; Tomography, Emission-Computed

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

8 patients with papillary cancer (4 with metastases, 4 in remission), 7 follicular cancer patients (6 with metastases), 2 patients with anaplastic thyroid cancer and 4 other non-medullary thyroid cancer patients all received an intravenous bolus injection of 220 MBq [111In-DTPA-D-Phe1]octreotide. Planar anterior and posterior gamma camera images of head-neck, chest and abdomen were obtained 24 and 48 h after injection. All primary cancers showed [111In-DTPA-D-Phe1] octreotide uptake; none occurred in patients in remission. The results were compared with conventional radio-iodine scintigraphy in patients with metastasised, differentiated thyroid cancer.

Topics: Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Humans; Indium Radioisotopes; Neoplasm Metastasis; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Terbium; Thyroid Neoplasms

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

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 purpose of this study was to evaluate the potential for therapy of thyroid tumors using the radiolabeled somatostatin (SS) analog octreotide.. Concentrations of 111In activity in human thyroid tumors and normal thyroid tissue and blood samples were determined 1-15 d after intravenous injection of 111In-diethylenetriaminepentaacetic acid-Phe1-octreotide. The results were compared with SS receptor (sstr subtype profile (by Northern blot analysis) and the relative expression of the second subtype, sstr2 (by ribonuclease protection assay, RPA). The true tumor volumes in lymph node metastases from 1 patient were estimated. In total, tissues from 68 patients were included in the study.. The highest tumor-to-blood ratio (T/B) for medullary thyroid carcinoma (MTC) was 360; for follicular adenoma (FA), 190; for Hurthle cell adenoma (HCA), 140; and for Hurthle cell carcinoma (HCC) and papillary carcinoma (PC), 70. The corresponding value was 7-18 for normal thyroid tissue, with higher values for colloid goiter (8-48) and thyroiditis (7-120). A high T/B was related to a large fraction of tumor cells in lymph node metastases. T/Bs were higher for the tumor samples with expression of sstr2 at Northern blot analysis than for those without. All thyroid tumor types regularly expressed sstr1, sstr3, sstr4, and sstr5. sstr2 was expressed in most MTC tumors but was not detected in FA or PC and was irregularly expressed in HCA and HCC. However, RPA analysis detected sstr2 in all tumors studied.. Despite the lack of sstr2 at Northern blot analysis in most of the thyroid tumors studied, high T/Bs were in general found when compared with corresponding values for normal thyroid tissue. The sometimes extremely high ratios are promising and indicate a possibility of using radiolabeled octreotide for radiation therapy of sstr-positive tumors in the future.

Topics: Blotting, Northern; Humans; Indium Radioisotopes; Lymphatic Metastasis; Octreotide; Pentetic Acid; Radiopharmaceuticals; Receptors, Somatostatin; RNA, Messenger; Thyroid Gland; Thyroid Neoplasms

Ten consecutive patients with Hürthle cell lesions of the thyroid (nodule/adenoma/carcinoma) were studied by (111)In-DTPA-D-Phe1-octreotide scintigraphy. Octreotide scintigraphy localized the primary Hürthle cell tumour in eight patients as distinct areas of increased uptake of radionuclide. Two patients with Hürthle cell carcinoma, previously thyroidectomized, had their metastases visualized by octreotide scintigraphy. Northern analyses showed expression of multiple somatostain receptor subtypes. Visualization of the Hürthle cell tumour may be due to a higher expression of somatostatin receptors in the lesions than in surrounding normal thyroid tissue. The tissue/blood (111)In concentration ratios for tumour samples from five patients showed clearly higher values than observed for normal connective tissue, muscle or lymph nodes. A relatively high uptake of (111)In was also observed in goiter tissue, which may lead to misinterpretations. The main indication for octreotide scintigraphy in patients with Hürthle cell carcinoma is suspicion of metastatic disease.

Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Blotting, Northern; Female; Humans; Indium Radioisotopes; Male; Middle Aged; Neoplasm Proteins; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; RNA, Messenger; Thyroid Neoplasms

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

Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.

Topics: Adenoma, Oxyphilic; Aged; Humans; Indium Radioisotopes; Male; Middle Aged; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Thyroid Neoplasms

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

111In-radiolabelled (DTPA-D-Phe1)-octreotide scintigraphy can be used to localize neuroendocrine tumours expressing somatostatin receptors (SSTRs). The aim of this paper was to analyse the importance of tumour volume and growth for the visualization by SSTR scintigraphy of metastases from medullary thyroid carcinoma (MTC).. Serum calcitonin concentrations were used to estimate volume and growth rate of MTC. Twenty-two patients who had persistent hypercalcitoninaemia after total thyroidectomy for MTC, indicating the presence of metastases, were studied.. SSTR scintigraphy visualized 15 tumours in 11 patients. Patients with scintigraphically visualized tumours had higher serum calcitonin and carcinoembryonic antigen concentrations and larger tumours, and the serum calcitonin concentration increased more rapidly with time. Tumour-associated symptoms and death from MTC occurred only in patients with scintigraphically visualized tumours.. Scintigraphically visualized tumours grow more rapidly and are more aggressive than nonvisualized lesions. SSTR scintigraphy can be helpful in the planning of palliative surgery for MTC and for diagnosing distant metastases, but cannot localize microscopic metastases.

Topics: Blotting, Northern; Female; Humans; Immunohistochemistry; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia Type 2a; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Thyroid Neoplasms; Thyroidectomy

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

Radioiodine scintigraphy is the gold standard exploration for imaging metastases of differentiated thyroid cancer and enables the decision of therapy with 131 radioactive iodine to be made. However, other approaches may be of use for diagnosis when there is no visible uptake after the administration of 131I, while elevated thyroblobulin levels suggest the presence of metastatic tissue in one third of metastatic patients. In order to detect recurrences or metastases, in conjunction with conventional imaging techniques (cervical and hepatic ultrasonography, lung CT scan..), other scintigraphic explorations with various radiopharmaceutics may be used, although none of them has any specificity towards thyroid cancer. Tl201 and MIBI which are used as perfusion tracers for myocardial explorations, are also used for detection of various tumors and for metastatic thyroid cancer. The performances of both radiopharmaceutics in imaging metastases are differently evaluated between investigators with a sensitivity ranging from 45 to 94% while the specificity varies less (82-97%). 18-Fluoro-deoxyglucose is retained in malignant tissue depending on the grade of malignancy. It has been shown to accumulate in thyroid cancer and metastases. Its detection by whole body PETscan represents a limitation for use which will be modified by new techniques. 111In-octreotide which binds to somatostatin receptors located on tumor cell membranes is able to show thyroid cancer metastases in some instances. We report on the very preliminary results of these combined scintigraphic approaches, performed in a limited number of patients who had no radioiodine uptake and elevated Tg levels, in order to determine the most appropriate exploration in terms of performance and cost.

Topics: Adenocarcinoma; Carcinoma, Papillary; Deoxyglucose; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Neoplasm Metastasis; Octreotide; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Thallium; 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

Somatostatin receptor scintigraphy (SRS) was evaluated in 25 differentiated thyroid carcinoma (DTC) patients. All DTC patients had elevated thyroglobulin levels. A total body scan (TBS) was performed 4 and 24 h after injection of indium-111-DTPA-Phe-octreotide. Group 1 included 16 patients with negative 131I TBS; group 2 had 9 patients with positive 131I TBS. SRS results were compared to the results of conventional imaging methods in group 1 and to 131I TBS in group 2. 131I TBS was performed after administration of a therapeutic dose of 131I in all patients except one. SRS was positive in 20 of 25 (80%) patients. In group 1, SRS was positive in 12 of 16 patients; in the 3 patients with no previously known tumor site, SRS visualized one abnormal neck focus of uptake in two. In the other 13 patients, SRS disclosed unknown mediastinal foci in 2, but visualized less organ involvements and a smaller number of tumor sites than conventional imaging methods. In group 2, SRS was positive in 8 of 9 patients and visualized an identical (7 patients) or a smaller number (1 patient) of involved organs than 131I TBS; in 2 patients, SRS allowed the discovery of 1 abdominal and 1 bone tumor site. We suggest than SRS should guide imaging modalities in DTC patients with negative 131I TBS and be an alternative to 131I TBS in DTC patients unable to withdraw T4 treatment.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Indium Radioisotopes; Iodine Radioisotopes; Lymphatic Metastasis; Male; Middle Aged; Octreotide; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Thyroglobulin; Thyroid Neoplasms

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

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

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

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

The general features of the biodistribution of the labeled somatostatin analog 111In-pentetreotide are already known. We describe some details of 111In-pentetreotide accumulation in the thyroid gland, mammae, spleen and gastrointestinal tract with respect to endocrine parameters, kinetics and time of imaging. In addition, dose estimations were performed for liver, spleen and kidney in patients without neuroendocrine tumor load and in patients with large tumors positive for somatostatin receptors. The overall absorbed dose turned out to be within the range reported previously. However, in patients with extensive tumor burden the radiation dose in liver, spleen and kidney tended to be lower than in patients without such malignancy. The dependence of estimated organ doses on the presence of somatostatin receptor-expressing tumors will have to be considered if radiotherapy with suitable labeled somatostatin analogs becomes available.

Topics: Biomarkers, Tumor; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Receptors, Somatostatin; Recurrence; Thyroid Neoplasms; Tissue Distribution

In a prospective study, 18 patients with recurrent medullary thyroid carcinoma (MTC) underwent magnetic resonance imaging (MRI) of the neck and mediastinum and somatostatin receptor scintigraphy (SRS) with 111In-labeled pentetreotide. In nine patients with macroscopic MTC, 17 corresponding lesions were found on MRI and SRS; in addition, 13 suspicious lesions were seen on SRS only. Histological confirmation was available for 19 metastatic lesions, showing MRI to be true positive in 13 metastases, SRS in 18. In minimal residual disease (n = 10), MRI and SRS were compared with the histological findings in three patients and with selective venous catheterization (SVC) in seven patients. Corresponding findings on MRI and SVC were seen in one of seven, whereas SRS and SVC showed concordant localization of tumor recurrence in five of seven. Histological examination demonstrated MTC tissue in one of three cases; MRI and SRS were false positive in one of three cases, while in the others the interpretation remained uncertain. In conclusion, SRS is a promising imaging modality for localization of MTC recurrence. MRI provides better spatial resolution and thus facilitates the planning of surgery for macroscopic metastases. In minimal residual disease, SRS turned out to be superior in detecting occult MTC recurrence, confirming SVC findings.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Indium Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Octreotide; Pentetic Acid; Receptors, Somatostatin; Thyroid Neoplasms; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

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