68 Ga-DOTATATE PET and functional imaging in pediatric pheochromocytoma and paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors in childhood. Up to 40% of PPGL are currently thought to be associated with a hereditary predisposition. Nuclear medicine imaging modalities such as fluorodeoxyglucose positron emission tomography (18 F-FDG PET), 68 Ga-DOTATATE PET, and 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy play an essential role in the staging, response assessment, and determination of suitability for targeted radiotherapy in patients with PPGL. Each of these functional imaging modalities targets a different cellular characteristic and as such can be complementary to anatomic imaging and to each other. With the recent US Food and Drug Administration approval and increasing use of 68 Ga-DOTATATE for imaging in children, the purpose of this article is to use a case-based approach to highlight both the advantages and limitations of DOTATATE imaging as it is compared to current radiologic imaging techniques in the staging and response assessment of pediatric PPGL, as well as other neuroendocrine malignancies.

Pheochromocytoma Diagnosed during the Treatment of Diffuse Alveolar Hemorrhage, a Diagnostic Necessity before Using High-dose Glucocorticoids.

A 46-year-old woman with exacerbating hemoptysis and dyspnea was diagnosed with diffuse alveolar hemorrhage (DAH). High doses of glucocorticoids were initiated, but afterward, paroxysmal hypertension (210/140 mmHg) with headache and abdominal pain appeared. A 50-mm left adrenal tumor with an intense uptake by iodine-123 metaiodobenzylguanidine scintigraphy and catecholamine hypersecretion revealed complication with pheochromocytoma. Because high doses of glucocorticoids, sometimes required for DAH, can provoke life-threatening paroxysmal hypertension in pheochromocytoma and paraganglioma (PPGL), our case suggests that PPGL needs to be recognized as the cause of DAH and should be detected with whole-body imaging before starting glucocorticoids.

High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.

Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.

[Non-secreting paraganglioma retroperitoneal]. / Paragangliome non sécrétant rétropéritonéal: à propos d'une observation.

Non-functional retroperitoneal paragangliomas are rare tumors. They are often asymptomatic and can reach very large sizes. We report the case of a 49-year old woman with retroperitoneal tumor detected during CT scan examination performed to find the cause of non-specific abdominal pain. Malignant forms, more frequent than benign forms, show locoregional invasion and are characterized by delayed-onset metastases. The treatment of these tumors is based on the most complete degree of surgical resection, since prognosis depends on it. There is no consensus on the usefulness of complementary therapies which may nevertheless constitute a supportive treatment.

Comparison of diagnostic value of I-123 MIBG and high-dose I-131 MIBG scintigraphy including incremental value of SPECT/CT over planar image in patients with malignant pheochromocytoma/paraganglioma and neuroblastoma.

PURPOSE: to compare lesion detectability of I-123 MIBG scintigraphy with that of high-dose I-131 MIBG and to evaluate incremental benefit of SPECT/CT over planar image for the detection and localization of the lesions in patients with I-131 MIBG therapy for malignant pheochromocytoma/paraganglioma and neuroblastoma. MATERIALS AND METHODS: we retrospectively investigated 16 patients with malignant pheochromocytoma/paraganglioma and neuroblastoma, who were referred for I-131 MIBG therapy. We investigated the lesion detectability in 10 pairs of I-123 and high-dose I-131 MIBG studies of the same patient, obtained within 2 weeks. In 31 studies of I-123 MIBG scintigraphy in 16 patients and 17 studies of high-dose I-131 MIBG scintigraphy in 12 patients, we compared planar and SPECT/CT images for the lesion detectability and localization. RESULTS: the number of lesions detected by I-123 MIBG planer image and SPECT/CT and high-dose planer I-131 MIBG and SPECT/CT were 3.0 and 3.7, 7.3 and 7.7 per study, respectively. SPECT/CT images provided additional diagnostic information over planar images in 25 studies (81%) of 12 patients (75%) in I-123 MIBG scintigraphy and in 9 studies (53%) of 9 patients (75%) in high-dose I-131 MIBG scintigraphy. CONCLUSION: post-therapy high-dose I-131 MIBG scintigraphy is superior to I-123 MIBG scintigraphy in lesion detectability even in comparison with I-123 MIBG SPECT/CT images and high-dose I-131 MIBG planar images in patients with malignant neuroendocrine tumors. SPECT/CT images are helpful for accurate identification of anatomic localization compared with planar images.

Whole-body iodine-131 metaiodobenzylguanidine imaging for detection of bone metastases in patients with paraganglioma: comparison with bone scintigraphy.

Iodine-131 metaiodobenzylguanidine ((131)I-MIBG) therapy is an effective treatment for patients with malignant paraganglioma for which surgical resection is not indicated. We performed high-dose (131)I-MIBG therapy on two patients with malignant paraganglioma and multiple bone metastases. The bone metastases were diagnosed by magnetic resonance imaging (MRI). Metastatic bone lesions were evaluated by whole-body (131)I-MIBG imaging and bone scintigraphy. Whole-body (131)I-MIBG imaging showed extensive metastatic bone lesions, whereas conventional bone scintigraphy did not. There was a remarkable discrepancy between (131)I-MIBG imaging and bone scintigraphy in the diagnosis of metastatic bone lesions of malignant paraganglioma in our two patients. High-dose (131)I-MIBG imaging may detect early stages of bone metastases, compared with bone scintigraphy, in patients with malignant paraganglioma.

Are somatostatin analogs therapeutic alternatives in the management of head and neck paragangliomas?

BACKGROUND: Although mostly benign, head and neck paragangliomas require active management because of injury to adjacent neurovascular structures. Surgery, usually preceded by embolization, allows for complete tumor removal. However, surgery carries a significant risk of iatrogenic injury, related to tumor volume. Because paragangliomas express somatostatin receptors with high density, we investigated the effect of a long-acting somatostatin analogue (OCT-LAR) on the size of such tumors to reduce iatrogenic injury and related the percentage of tumor shrinkage to a tracer uptake index calculated on somatostatin receptor scintigraphy (SRS). METHODS: In eight of the first nine patients, 30 mg of OCT-LAR was given intramuscularly every 28 days for 3 doses; one patient withdrew after the first dose because of side effects. Conventional imaging with computed tomography (CT) scan or magnetic resonance imaging plus SRS revealed 18 paraganglioma sites. For each lesion, a tracer uptake index was calculated on pretreatment SRS. All 18 tumors were measured by CT scan before treatment and 1 month after the third injection. RESULTS: The average percent tumor shrinkage was 4.0 +/- 10.0%, and the average tumor reduction was 1.0 +/- 3.8 cm (P = .27, NS). Only 2 of the 18 paragangliomas shrank by more than 20%; these two tumors belonged to the only one secreting patient. There was no significant relation between tracer uptake index and tumor response. CONCLUSION: These results suggest 1) that SRS results do not predict OCT-LAR efficacy on paraganglioma size, and 2) OCT-LAR is not useful in the preoperative management of paragangliomas.

Interventional radiology in Carney triad.

Interventional therapeutic methods are presented in Carney triad, which is a syndrome defined as the simultaneous presence of gastric leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary chondroma. The paragangliomas in the carotid bifurcation and the mediastinum were successfully treated via transarterial embolization with particles. Three intrapulmonary chondromas were ablated using MRI-guided laser-induced thermotherapy (LITT) after previous devascularization via transvenous pulmonary particle embolization. In summary, interventional techniques could be a therapeutic option in patients suffering from Carney triad.

Comparison of somatostatin analog and meta-iodobenzylguanidine radionuclides in the diagnosis and localization of advanced neuroendocrine tumors.

A comparison has been made of [(123)I]meta-iodobenzylguanidine ([(123)I]MIBG) and [(111)In]pentetreotide scintigraphy in 54 patients with a variety of neuroendocrine tumors of whom 46 patients had metastatic disease. [(111)In]Pentetreotide scintigraphy was more sensitive in detecting metastatic lesions, as demonstrated on computed tomography and/or magnetic resonance scanning, than [(123)I]MIBG: 67% vs. 50% for carcinoid tumors (n = 24), 91% vs. 9% for pancreatic islet cell tumors (n = 12), 100% vs. 60% for medullary thyroid carcinomas (n = 5), and 75% vs. 100% for pheochromocytomas/paragangliomas (n = 4). In only 2 patients were lesions seen with [(123)I]MIBG scanning that were not apparent with [(111)In]pentetreotide. With the exception of pancreatic islet cell tumors, both radionuclides exhibited a similar sensitivity in detecting hepatic metastases, whereas in three patients the two radionuclides exerted a complementary role as different deposits exhibited uptake to only 1 or the other radionuclide. Hepatic metastases were the most important clinical predictor of a positive scan for both radionuclides. Neither elevated 5-hydroxyindoleacetic acid levels nor any other hormonal marker was predictive of a positive scan. In 8 patients with clinical and/or hormonal evidence of a neuroendocrine tumor but negative conventional radiology, [(111)In]pentetreotide scintigraphy was more sensitive than [(123)I]MIBG (37.5% vs. 12.5%) in detecting lesions. In conclusion, scintigraphy with [(111)In]pentetreotide detects more metastatic lesions than [(123)I]MIBG in patients with carcinoid and pancreatic islet cell tumors and medullary thyroid carcinomas; [(123)I]MIBG scintigraphy may be more sensitive for sympathoadrenomedullary tumors. The radionuclides may exert a complementary role in the detection and treatment of neuroendocrine tumors in occasional patients, as areas of different pattern of uptake were identified within the same patient. These data have implications not only for staging such tumors, but also for identifying patients who might benefit from treatment using either [(131)I]MIBG or radioactive somatostatin analogs.

Iodine-131-metaiodobenzylguanidine scintigraphy in preoperative and postoperative evaluation of paragangliomas: comparison with CT and MRI.

Iodine-131-metaiodobenzylguanidine (MIBG) scintigraphy, transmission computed tomography and magnetic resonance imaging were used to evaluate 36 patients with clinically suspected functioning paragangliomas. The patients were divided into two groups. In Group 1 (n = 21), studied before surgery, patients mainly had benign adrenal disease. In Group 2 (n = 15), studied after surgery, patients frequently had malignant or extra-adrenal tumors. In Group 1, transmission computed tomography and magnetic resonance imaging were more sensitive (100% for both) than MIBG scintigraphy (82%), which, however, was the most specific (100%). In Group 2, MIBG scintigraphy and magnetic resonance imaging were more sensitive (83% for both) than transmission computed tomography (75%), but MIBG was again the most specific (100%). Thus, all three were complementary modalities for localizing paragangliomas both preoperatively and postoperatively. MIBG imaging is indicated for both groups but it is especially recommended for postsurgical patients with recurrence because the disease is often malignant or extra-adrenal.

CT evaluation of enhancing mediastinal masses.

The CT scans of 132 patients with mediastinal masses and CT scans from our teaching file were retrospectively reviewed to evaluate the role of contrast enhancement in limiting the differential diagnosis of a mediastinal mass. Ten patients with an enhancing mediastinal mass were found. Coupled with mass enhancement, location and hypertension were helpful in limiting the differential diagnosis. Four masses were of thyroid origin, and all were contiguous with neck thyroid. All patients with functioning paragangliomas were hypertensive and all intrapericardial enhancing masses were functioning paragangliomas. A normotensive patient had a nonfunctioning aortic body paraganglioma superiolateral to the aortic arch. An enhancing mass in a similar location in a hypertensive patient was a functioning paraganglioma. Castleman disease occurred posterior to the heart.

[The enlarged retrorectal space--indicative of specific pathology or only unspecific symptom of disease in the true pelvis? (author's transl)]. / Der erweiterte Retrorectalraum--ein sicher pathologisches oder nur unspezifisches Zeichen einer Erkrankung im kleinen Becken?

The retrorectal space was measured on the lateral view of the rectum during double contrast barium enema examination in 300 patients in whom no abnormality of the rectum, sacrum or in the true pelvis was demonstrated clinically or radiographically. The measurement obtained is the distance between posterior wall of the rectum and the anterior surface of the sacrum between S2 and S5. The measurements at S5 are considered most accurate, since at this level the rectum will be positively in midline. The normal width at S5 is between 0.2 and 1.5 cm. In connection with other symptoms, a distance between 1.5 and 2 cm should be regarded as suspicious and above 1 cm as definitely abnormal, as was demonstrated in 95 cases with diffuse and localized enlargement of the retrorectal space. An abnormal measurement of greater than 2 cm however is an unspecific symptom and should not by itself be considered indicative of specific pathology, but rather should lend supporting evidence to other abnormal findings in the true pelvis.