In-111 Pentetreotide Research Articles

Large-cell neuroendocrine carcinoma of the lung: A clinicopathologic study of eighteen cases and the efficacy of adjuvant treatment with octreotide

This study was undertaken to evaluate the efficacy of a new adjuvant protocol with octreotide, alone or in combination with radiotherapy, in radically resected large cell neuroendocrine carcinomas of the lung. Between 1990 and 2001, a total of 18 consecutive patients affected by large cell neuroendocrine carcinomas of the lung were operated on. Lobectomy and systemic lymphadenectomy were performed in all cases. Postoperative radiotherapy was performed when stage was higher than Ib. Ten patients with positive results of preoperative indium In-111 pentetreotide scintigraphy received octreotide after the operation. Nine patients (50%) had local recurrences or distant metastases (mean recurrence time 14 months); palliative chemotherapy was given, but all patients died. In 10 cases (55.5%) octreotide alone or in combination with radiotherapy was administered as adjuvant treatment; 9 of these patients (90%) are alive and free of disease ( P = .0007), and the other had liver and brain metastases 21 months after surgery. Our preliminary results seem to demonstrate the efficacy of octreotide as adjuvant therapy in large cell neuroendocrine carcinomas of the lung when results of preoperative indium In-111 pentetreotide scintigraphy were positive. Further study are required to assess the utility of octreotide in patients with negative results of indium In-111 pentetreotide scintigraphy.

Ectopic Acromegaly: Localization of the Pituitary Growth Hormone-Releasing Hormone Producing Tumor by In-111 Pentetreotide Scintigraphy and Report of Two Cases

Acromegaly is habitually caused by a pituitary growth hormone (GH)-secreting adenoma, resulting in elevated circulating levels of GH and insulinlike growth factor-1 (IGF-1). Ectopic acromegaly is of very rare occurrence, accounting for less than 1% of clinical acromegaly. This entity is more often than not related to a pancreatic or bronchial GH-releasing hormone (GH-RH) producing neuroendocrine tumor, which is responsible for a nonadenomatous hyperplasia of the pituitary somatotrophic cells. The authors report 2 cases of successful detection of a GH-RH-secreting tumor by In-111 pentetreotide scintigraphy, one in a lung and the other in the pancreas.

Laryngeal Paraganglioma: An Updated Critical Review

Laryngeal paragangliomas are rare submucosal lesions that arise from paraganglion cells located in the false vocal fold and subglottic larynx. To date, 76 recognized cases have been reported in the world literature. Symptoms arise when the lesions become large enough to impair function. Supraglottic paragangliomas cause hoarseness and deglutition disorders, whereas subglottic tumors become symptomatic when they obstruct the airway. Evaluation of these tumors includes obtaining a complete history. Familial paragangliomas and hypertension should be sought but are rarely, if ever, associated with laryngeal paragangliomas. MRI can detect these lesions and permit characterization of the vascularity of the lesion. Adding 111In pentetreotide scanning can distinguish neuroendocrine tumors from other submucosal laryngeal lesions, making the preoperative diagnosis clearer and obviating the need for biopsy. The biggest dilemma regarding laryngeal paragangliomas is making the correct pathologic distinction between paraganglioma, typical carcinoid, atypical carcinoid and medullary thyroid cancer. Immunohistochemical markers, supplementing standard histopathologic evaluation, can distinguish paragangliomas from the aforementioned tumors. This distinction is critical as the prognosis for treated paragangliomas is excellent compared to that for other neuroendocrine neoplasms. Almost all alleged malignant paragangliomas of the larynx are in reality atypical carcinoid tumors that have been misdiagnosed. Treatment should always comprise excision. Thyrotomy has the best chance of achieving a sustained cure without damaging phonation or deglutition. Laser excision has been used successfully but there is no great experience with this modality. Surgery is preferable to radiation for paragangliomas in all locations but especially so in the larynx, due to issues such as swelling, airway protection and destruction of cartilage. With increased clinical suspicion and the use of modern imaging techniques, laryngeal paragangliomas should be routinely diagnosed and treated without loss of laryngeal functions.

Indium-111 pentetreotide therapy in somatostatin receptor expressing neoplasms: Results from clinical practice

4269 Background: Therapeutic In-111 pentetreotide effectively controls symptoms in two-thirds of pts with hormonally active neuroendocrine neoplasms that overexpress the somatostatin receptor subtype 2. Auger electrons that are internalized into the nucleus provide cell-specific cytotoxicity. Renal excretion is the major route of elimination for In-111 pentetreotide. We hypothesized that In-111 pentetreotide therapy in community practice would not only offer an unmet medical need but provide an opportunity to further establish safety and efficacy of this particular form of radiolabeled somatostatin analog therapy. Methods: Between September 1999 and July 2003, pts undergoing therapeutic In-lll pentetreotide at Memorial Medical Center New Orleans, LA were included into this study. Clinical data including age, gender, diagnosis, date of diagnosis, prior treatment(s), hepatic and renal function were recorded. Serial data were collected for those pts receiving 2 or more In-111 pentetreotide therapies. Complete blood counts and differentials were reviewed. Creatinine clearance and survival were calculated as end measures of safety and efficacy, respectively. Results: 85 pts (46 females) were treated with an average dose of 487.9 mCi of In-111 pentetreotide during this 4-year period. The median age was 54.9 yrs. The majority of pts had a well-differentiated neuroendocrine tumor such as carcinoid or pancreatic islet cell carcinoma. 142 treatments were delivered with 41 pts receiving 2 or more treatments (28 pts were treated twice; 10 pts received 3 doses and 3 pts received 4 doses). The baseline creatinine clearance was 93 ml/min. For the 41 subjects treated on more than one occasion, subsequent creatinine clearances were 82.8, 95.2 and 81.9 ml/min following cumulative doses 493, 986 and 1,483 mCi, respectively. Treatment-related myelosuppression or myelodysplasia were not observed. The median survival was 22.1 mos from the time of the first In-111 pentetreotide treatment and 84.3 mos from the time of diagnosis. Conclusions: In-111 pentetreotide therapy can be safely administered in a community hospital setting. No significant financial relationships to disclose.

Indium-111 pentetreotide therapy in somatostatin receptor expressing neoplasms: Results from clinical practice

4269 Background: Therapeutic In-111 pentetreotide effectively controls symptoms in two-thirds of pts with hormonally active neuroendocrine neoplasms that overexpress the somatostatin receptor subtype 2. Auger electrons that are internalized into the nucleus provide cell-specific cytotoxicity. Renal excretion is the major route of elimination for In-111 pentetreotide. We hypothesized that In-111 pentetreotide therapy in community practice would not only offer an unmet medical need but provide an opportunity to further establish safety and efficacy of this particular form of radiolabeled somatostatin analog therapy. Methods: Between September 1999 and July 2003, pts undergoing therapeutic In-lll pentetreotide at Memorial Medical Center New Orleans, LA were included into this study. Clinical data including age, gender, diagnosis, date of diagnosis, prior treatment(s), hepatic and renal function were recorded. Serial data were collected for those pts receiving 2 or more In-111 pentetreotide therapies. Complete blood counts and differentials were reviewed. Creatinine clearance and survival were calculated as end measures of safety and efficacy, respectively. Results: 85 pts (46 females) were treated with an average dose of 487.9 mCi of In-111 pentetreotide during this 4-year period. The median age was 54.9 yrs. The majority of pts had a well-differentiated neuroendocrine tumor such as carcinoid or pancreatic islet cell carcinoma. 142 treatments were delivered with 41 pts receiving 2 or more treatments (28 pts were treated twice; 10 pts received 3 doses and 3 pts received 4 doses). The baseline creatinine clearance was 93 ml/min. For the 41 subjects treated on more than one occasion, subsequent creatinine clearances were 82.8, 95.2 and 81.9 ml/min following cumulative doses 493, 986 and 1,483 mCi, respectively. Treatment-related myelosuppression or myelodysplasia were not observed. The median survival was 22.1 mos from the time of the first In-111 pentetreotide treatment and 84.3 mos from the time of diagnosis. Conclusions: In-111 pentetreotide therapy can be safely administered in a community hospital setting. No significant financial relationships to disclose.

Functional-anatomical image fusion in neuroendocrine tumors.

Nuclear medicine provides physiologic and functional data for normal and pathologic organs but often the clear definition of the sites of radiotracers' uptake are difficult. Radiological methods are able to identify structural changes in a detailed way, but do not give precise information on function of organs or pathologic lesions. The registration and fusion of nuclear medicine studies with structural information obtained by radiological exams allows the precise correlation of functional and anatomical data. Software-based fusion of independently performed nuclear medicine and morphologic studies is uncertain of success and the alignment procedures are labor intensive. Recently, a new imaging device combining a dual-head, variable angle gamma camera with a low-dose x-ray tube has been introduced; the acquired single-photon emission computed tomography (SPECT) and x-ray computed tomography (CT) images are coregistered by means of the hardware in the same session. This new technology can be particularly useful when applied to scintigraphic procedures in neuroendocrine tumors. In-111 pentetreotide and radiolabeled MIBG play an important role in the study of patients with these tumors; the addition of anatomical maps provides a precise localization of SPECT findings and allows the exclusion of disease in sites of physiologic tracer uptake. SPECT/CT fused images are able to provide additional information that improves the accuracy of SPECT interpretation and leads to changes in therapeutic options, so enhancing the clinical role of nuclear medicine in evaluating patients with neuroendocrine tumors.

Valoración de un tumor neuroendocrino mediante gammagrafía con 111In-pentetreótido y PET con 18F-FDOPA y 18F-FDG

We present the case of a 67 year old patient diagnosed of a neuroendocrine carcinoid tumour of the small intestine. The tumour and subsequent metastases were resected previously by surgery, but a new recurrence was suspected. CT showed left adrenal enlargement. 18F-FDG PET was normal and 111In pentetreotide scintigraphy showed liver and left diaphragmatic uptake. 18F-FDOPA PET showed uptake foci in liver and left diaphragm and also in left adrenal gland, retro urinary bladder area and multiple foci in abdominopelvic region, suggesting a peritoneal carcinomatosis. 18F-FDOPA PET was the first imaging modality to assess the extensiveness of the disease that was confirmed six month later by CT. Neuroendocrine tumors are a heterogeneous group of neoplasia. They are studied by conventional radiologic and functional techniques of nuclear medicine. This case illustrates the need to use the different techniques and tracers according to the characteristics of the tumor to be studied to thus improve the diagnostic and prognostic performance.

Effect of Geometry in the Radiochemical Purity Analyses of Tc-99 m Mertiatide and In-111 Pentetreotide

Effect of Geometry in the Radiochemical Purity Analyses of Tc-99 m Mertiatide and In-111 Pentetreotide

Octreotide imaging plus bone scintigrams to optimally localize gastroenteropancreatic neuroendocrine tumors.

In-111 pentetreotide (Octreotide) is highly sensitive for detecting gastroenteropancreatic neuroendocrine tumors and their metastases. However, a lack of landmarks makes it difficult to localize them anatomically. To overcome this difficulty, the authors simultaneously obtained Octreotide and bone tomoscintigrams, in addition to standard planar images. They used a bicolor scale to display pairs of scintigrams to easily identify the distribution of both tracers. Twenty-one hours after Octreotide injection, Tc-99m MDP was also administered to the patients. Three hours later, dual-energy planar and tomographic data were acquired simultaneously. The latter were reconstructed using a filtered back-projection algorithm using a Metz filter. Both sets of data were displayed simultaneously using a bicolor scale, such that Octreotide data appear in green and bone data in red. Planar, tomographic, and three-dimensional data were obtained. With this approach, foci of abnormal uptake are localized more precisely. Hard data can be transmitted easily to referring physicians, who appreciate this compact and efficient means to locate foci of abnormal uptake, especially during surgery planning. However, this method is not well suited to the visualization of small lesions with low Octreotide uptake because the intensity range is drastically reduced. Such lesions are better seen on Octreotide planar images and standard tomoscintigrams. This approach, which involves only standard image processing, provides landmarks to easily localize significant Octreotide uptake. It can be implemented readily in most nuclear medicine workstations. It complements but does not replace the usual method to display Octreotide data.

Radiopeptides from diagnosis to therapy

Radiopeptides are playing an increasing role in the diagnosis of disease. Initially based on the somatatostatin system, early research concentrated on identifying tumours of neuroendocrine origin. New techniques with artificial peptides are extending their role into other areas such as thrombus formation and heart disease. It has been shown that radiopeptides have excellent labelling new methods have looked at therapy starting with high activities of In-111 pentetreotide to the development of Y-90 based products and new and novel peptides and radio isotopes. Outside of PET there are the most exciting developments in nuclear medicine.

"Raccoon eyes" revisited: diagnostic imaging of neuroblastoma with In-111 pentetreotide.

Neuroblastoma, the most common extracranial cancer of childhood, is a potentially lethal neoplasm of sympathetic nervous tissue origin. Radiologic diagnosis and staging is usually achieved with computed tomography (CT), magnetic resonance imaging (MRI), and scintigraphy using Tc-99m MDP and I-131 metaiodobenzylguanidine (MIBG). The authors describe a child with bilateral periorbital ecchymosis and proptosis who was presumed to have neuroblastoma originating from the right adrenal gland and who underwent metastatic evaluation with In-111 pentetreotide.

Buttock granulomas: a consequence of intramuscular injection of Sandostatin detected by In-111 octreoscan.

A 64-year-old woman with a malignant carcinoid tumor began receiving monthly treatment with 30 mg long-acting Sandostatin suspension injected intramuscularly in the buttocks along with 200 μg Sandostatin (Novartis, Hanover, NJ) subcutaneously once per day in 1994. Tc-99m MDP bone imaging showed areas of extensive metastases. To better characterize the extent of disease, In-111 pentetreotide imaging was performed, with images acquired at 24 hours. In addition to widespread disease, unusual uptake was shown in the upper outer quadrants of both buttocks, apparently at the sites of intramuscular Sandostatin injection. Recent studies of single-dose intramuscular injections have shown that Sandostatin injection may lead to localized granulomatous myositis and granuloma formation. In this patient, two large areas of increased uptake located in both buttocks are seen at the sites of repeated intramuscular injection of Sandostatin.

High-Dose Indium 111In Pentetreotide Radiotherapy for Metastatic Atypical Carcinoid Tumor*

Indium In 111 pentetreotide imaging of neuroendocrine tumors that overexpress somatostatin receptors has become standard for localization of these tumors. This radioligand is internalized into the cell and can induce receptor-specific cytotoxicity by emission of Auger electrons. We hypothesized that high-dose 111In-pentetreotide could be therapeutic in patients with somatostatin receptor-expressing tumors. Our 35-year-old patient had atypical carcinoid tumor metastatic to cervical, supraclavicular, mediastinal, and mesenteric lymph nodes and to the liver and bone. Chemotherapy had stabilized the disease but with severe gastrointestinal side effects. After a diagnostic 111In-pentetreotide scan, the patient was given eight courses (180 mCi each) of 111In-pentetreotide therapy to selectively target somatostatin receptor-expressing tumor cells. The disease was stable for approximately 14 months. The patient had two additional courses of 111In-pentetreotide therapy (360 mCi each). She died of the disease approximately 18 months after initiation of 111In-pentetreotide therapy.

High-Dose Indium 111In Pentetreotide Radiotherapy for Metastatic Atypical Carcinoid Tumor*

Indium In 111 pentetreotide imaging of neuroendocrine tumors that overexpress somatostatin receptors has become standard for localization of these tumors. This radioligand is internalized into the cell and can induce receptor-specific cytotoxicity by emission of Auger electrons. We hypothesized that high-dose 111In-pentetreotide could be therapeutic in patients with somatostatin receptor-expressing tumors. Our 35-year-old patient had atypical carcinoid tumor metastatic to cervical, supraclavicular, mediastinal, and mesenteric lymph nodes and to the liver and bone. Chemotherapy had stabilized the disease but with severe gastrointestinal side effects. After a diagnostic 111In-pentetreotide scan, the patient was given eight courses (180 mCi each) of 111In-pentetreotide therapy to selectively target somatostatin receptor-expressing tumor cells. The disease was stable for approximately 14 months. The patient had two additional courses of 111In-pentetreotide therapy (360 mCi each). She died of the disease approximately 18 months after initiation of 111In-pentetreotide therapy.

In-111 pentetreotide imaging changes management of patients with gastrinoma

s: Abstracts of an International Conference on Peptide Radiopharmaceuticals in Diagnosis and Therapy Rome, Italy, 25-28 May 2000: Oral Presentations

Visualization of Paget's disease during somatostatin receptor scintigraphy.

Paget’s disease is a common bone disorder of unknown cause characterized by osteolysis and production of new bone with abnormal architecture. Somatostatin analog (octreotide) receptor scintigraphy localizes benign and malignant neoplastic processes, including neuroendocrine, nervous system, renal, and lymphomas, and other diseases, such as granulomatous disease, inflammatory bowel disease, fibrous dysplasia, and rheumatoid arthritis. Various subtypes of cellular surface somatostatin receptors have been described in different cell types, such as leukocytes, fibroblasts, vessels, and osteoblasts. In-111 pentetreotide uptake is associated with the expression of somatostatin receptor type II. We report two cases of In-111 pentetreotide uptake in radiographically demonstrable areas of Paget disease.

Somatostatin Receptor Scintigraphy of a Patient with a Giant Invasive Prolactinoma

A 41-year-old with a giant prolactinoma underwent in-111 pentetreotide (Octreotide) imaging showing very intense tracer uptake in the region of the anterior skull base. In contrast, there was no significant response to Octreotide therapy. Prediction of clinical responsiveness to Octreotide therapy in patients with pituitary adenomas may depend on the presence of somatostatin receptor subtype 5. Pentetreotide does not avidly bind to this receptor subtype and therefore, cannot be used clinically to predict therapeutic Octreotide responsiveness in patients with large prolactinomas.

Somatostatin receptor scintigraphy in a patient with an epigastric mass and multiple liver metastases.

A patient with an epigastric mass and multiple liver metastases with a histopathologic diagnosis of adenocarcinoma was treated with combined chemohormonal therapy. She had a poor response, despite intense and repeated treatment. Somatostatin receptor scintigraphy with In-111 pentetreotide demonstrated the presence of somatostatin receptors in the primary lesion and in the liver metastasis, suggesting the tumor was of neuroendocrine nature. This finding led to a sudden change in treatment as a result of the beneficial use of octreotide, and to a revision in the diagnosis with pathologic recognition of a carcinoid. This case underlines the clinical impact of somatostatin receptor scintigraphy in patient management by providing information on the somatostatin receptor status of the tumor.

Indium In-111 pentetreotide scintigraphy: application to carotid body tumors.

This study was conducted to investigate and illustrate the use of Indium In-111 pentetreotide scintigraphy as it applies to carotid body tumors (CBT). Localization has relied primarily on ultrasonography, computed tomography, and magnetic resonance imaging with angiographic confirmation. These methods only assess the cervical bifurcation without providing an evaluation of metastasis in patients without symptoms or recurrence in patients after surgery. Indium In-111 pentetreotide scintigraphy was used in five patients with a diagnosis of CBT. Four patients were evaluated after surgical excision for evidence of tumor recurrence. One patient was evaluated before excision for diagnostic confirmation. No evidence of tumor recurrence was demonstrated in the four patients who had undergone previous CBT excision. One of these patients had increased activity in the pituitary, later confirmed as an enlarged pituitary without evidence of an adenoma with computed tomography. The diagnosis of CBT was confirmed in the patient evaluated before surgery. This patient also had increased activity in the occipital region, confirmed as the site of previous ischemia on computed tomography. Indium In-111 pentetreotide scintigraphy is a new innovative method for viewing neuroendocrine tumors. Its potential lies not only in tumor localization but also in identification of recurrent tumor at the operative site and metastatic disease.

Receptor scintigraphy of non-neuroendocrine cancers with In-111 pentetreotide.

Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with neuroendocrine identities but also malignancies without neuroendocrine expression. Recently, the somatostatin analog pentetreotide was labeled with In-111 (OctreoScan 111, Mallinckrodt Medical BV, Petten, Holland) and introduced for the in vivo visualization in man of SR-positive tissues. In the present report, SR-specific scintigraphy is evaluated as a clinical tool for tissue characterization in correlation with histological and radiological examinations. Scintigraphy was focused and performed in cancer types without neuroendocrine tissue expression such as brain (n = 6) and breast tumors (n = 9) and lymphomas (n = 5). Scintigraphy was performed for comparison at 6 and 22 h after i.v. application of 111 MBq (3 mCi) of In-111-Pentetreotide. In the breast cancer group, the primary tumor was visualized in all 9 women as well as in all 4 cases with palpable axillary lymph nodes. Three women with a negative axillary node scan and impalpable nodes had positive biopsy. In two cases, mediastinal lymph node involvement was observed. So far the role of SR-positive breast cancer (BC) scans remains unknown. It is tempting to speculate that in resected women who are histologically and scintigraphically SR positive, it might be of value in the early detection of symptom-free recurrences. High densities of SR were present within both meningiomas, the high-grade astrocytoma and the craniopharyngioma. Differentiation of low- and high-grade astrocytomas could not be successfully achieved because both grades showed intense radioactivity uptake, even though high-grade tumors lack SR. The latter might be due to the damaged blood-brain barrier and the poor radioactivity washout observed in high-grade astrocytomas. All five lymphomas could be detected due to the presence of activated lymphocytes and macrophages that express SR at a sufficient density. In conclusion, SR scintigraphy in non-neuroendocrine malignancies does not seem to be reliable for an initial tumor staging but rather more suitable for a tissue characterization and extremely useful for monitoring changes of SR expression after treatment.