Iodine-131-MIBG therapy of a patient with carcinoid liver metastases

Iodine-13I-metaiodobenzylguanidine (MIBG) is highly concentrated by >60% of carcinoid metastases and thus provides a therapeutic opportunity. METHODS: A symptomatic patient with carcinoid liver metastases, unresponsive to chemotherapy combined with interferon-alpha, was subsequently treated with 131I-MIBG. RESULTS: Radionuclide therapy, which was without significant side effects, resulted in symptomatic improvement and reduced urinary 5-hydroxyindoleacetic acid levels. No new metastases were observed for 15 mo after 131I-MIBG therapy. Gross cystic change occurred in existing liver metastases, presumably as a result of ischemic necrosis. Surgical deroofing and aspiration of cysts led to regeneration of normal liver tissue. CONCLUSION: Iodine-131-MIBG therapy can provide prolonged symptomatic relief and improved quality of life in patients with metastatic carcinoid disease unresponsive to other therapies. The antitumor effect of 131I-MIBG was accompanied by few side effects, suggesting that this therapy should be considered in symptomatic patients with an early stage of disease.     

Acute liver necrosis induced by iodine-131-MIBG in the treatment of metastatic carcinoid tumors

Iodine-131-metaiodobenzylguanidine (MIBG) is used in the treatment of carcinoid tumors. Temporary palliation with complete subjective symptomatic response has been reported in these patients. This treatment is usually well tolerated and side-effects are generally limited to nausea, mild hepatic toxicity with spontaneous recovery and temporary myelosuppression. Our case report shows that repeated treatment with [131I]MIBG in a patient with extensive carcinoid liver metastasis may cause severe hepatic toxicity leading to death. Factors such as concomitant use of 5-fluorouracil and the progressive nature of the disease may have contributed to this event.     

Assessment of self-injurious behavior maintained by access to self-restraint materials

Metastatic tumor is one of several etiologies of space-occupying masses in the orbit that accounts for 1%-13% of all orbital masses (1). In the adult patient population, breast cancer is the most common tumor to metastasize to the orbit followed by metastases from the lung, prostate and gastrointestinal tract (2). It is rare for carcinoid tumors to metastasize to the eye or to the orbit. Carcinoid tumors arise from Kulchitsky cells that originate in the neural crest. Histologically, these tumors resemble, but are not as aggressive as, adenocarcinomas. Most carcinoids arise in the gastrointestinal tract or the lung. The most common site for carcinoid metastases is the liver. On anatomical imaging studies, such as CT and magnetic resonance imaging, metastatic orbital carcinoid tumors appear as nonspecific tumor masses. Carcinoid tumors have an affinity for uptake of the radiopharmaceutical 131I-metaiodobenzylguanidine (MIBG) (3). We report a case of a patient with a known carcinoid tumor who developed a left orbital mass that demonstrated abnormal uptake of 131I-MIBG indicative of metastatic carcinoid tumor to the orbit.     

Rate of insufficient samples for fine-needle aspiration for nonpalpable breast lesions in a multicenter clinical trial: The Radiologic Diagnostic Oncology Group 5 Study. The RDOG5 investigators

Metaiodobenzylguanidine (MIBG) was developed 18 yr ago for scintigraphic imaging of the adrenomedullary tumors pheochromocytoma and neuroblastoma. Many studies have shown the usefulness of this agent for the management of patients with neuroblastoma or pheochromocytoma, and the 131I-labeled form was recently approved by the Food and Drug Administration for use in the U.S. This article summarizes our current concepts on the diagnostic use of MIBG in children. The radioisotopes available for labeling of MIBG and related compounds, the dosimetry, metabolism and mechanisms of uptake and retention are discussed. Our protocols for imaging both 131I-MIBG and 123I-MIBG, along with the normal distribution of these compounds, are reviewed. The use of MIBG for the management of neuroblastoma, and comparisons with other radiotracers available for imaging neuroblastomas are also addressed.     

The elbow joint: osseous and ligamentous structures

PURPOSE: The analogue 131I-metaiodobenzylguanidine (MIBG), which is specifically targeted to neuroblastoma cells, may provide more effective and less toxic treatment for neuroblastoma than conventional external-beam radiotherapy. We report a dose escalation study of 131I-MIBG to define dose-limiting toxicity without and with autologous bone marrow support. PATIENTS AND METHODS: Thirty patients with relapsed neuroblastoma were treated in groups of six with escalating doses of 3 to 18 mCi/kg of 131I-MIBG. After rapid escalation in the first three patients treated at 3 to 6 mCi/kg, treatment was escalated in 3-mCi/kg increments from 9 to 18 mCi/kg. Autologous tumor-free bone marrow was cryopreserved in all patients receiving 12 mCi/kg and more. Toxicity and response were assessed. RESULTS: Eighty percent of patients who received 12 mC/kg or more experienced grade 4 thrombocytopenia and/or neutropenia. Dose-limiting hematologic toxicity was reached at 15 mCi/kg, at which level two of five assessable patients required bone marrow reinfusion for absolute neutrophil count (ANC) of less than 200/microL for more than 2 weeks, and four of nine at the 18-mCi/kg level. Prolonged thrombocytopenia was common, with failure to become platelet-transfusion independent in nine patients. One patient with extensive prior treatment developed secondary leukemia and three became hypothyroid. Responses were seen in 37% of patients, with one complete response (CR), 10 partial response (PR), three mixed response, 10 stable disease, and six progressive disease. The minimum dose of 131I-MIBG for 10 of the 11 responders was 12 mCi/kg. CONCLUSION: Treatment with 131I-MIBG has mainly hematologic toxicity, which can be abrogated with bone marrow rescue. The high response rate in refractory disease suggests that this agent may be useful in combination with myeloablative chemotherapy and autologous stem-cell rescue to improve outcome in advanced neuroblastoma.     

Validation of the full and short forms of the CAMDEX interview for diagnosing dementia: evidence from a one-year follow-up study

BACKGROUND: Metaiodobenzylguanidine (MIBG) labeled with 131I has been used for targeted radiotherapy of neural crest tumors, with bone marrow suppression being the primary dose-limiting toxicity. The purpose of this study was to examine the engraftment and toxicity of higher myeloablative doses of 131I-MIBG with autologous bone marrow support. PROCEDURE: Twelve patients with refractory neuroblastoma were given infusions of their autologous, cryopreserved bone marrow following 1-4 doses of 131I-MIBG. The median cumulative administered activity per kilogram of 131I-MIBG was 18.0 mCi/kg (range 14.1-50.2 mCi/kg), the median total activity was 594 mCi (range 195-1,353 mCi), and the median cumulative whole body irradiation from 131I-MIBG was 426 cGy (range 256-800 cGy). A median of 2.5 x 10(8) viable cells/kg (range 0.9-4.7 x 10(8) cells/kg) was given in the bone marrow infusion. RESULTS: All 12 patients achieved an absolute neutrophil count > 500/microliter with a median of 19 days, but only 5/11 evaluable patients achieved red cell transfusion independence, in a median of 44 days; and 4/11 evaluable patients achieved platelet count > 20,000/microliter without transfusion, in a median of 27 days. CONCLUSIONS: Autologous bone marrow transplantation may allow complete hematopoietic reconstitution following ablative 131I-MIBG radiotherapy in patients with neuroblastoma. Risk factors for lack of red cell or platelet recovery include extensive prior chemotherapy, progressive disease at the time of transplant, especially in the bone marrow, and a history of prior myeloablative therapy with stem cell support.     

Sympathetic tone assessed by washout of iodine 125-labeled metaiodobenzylguanidine from the murine left ventricle--influence of immobilization stress and inhibition of the renin-angiotensin system

BACKGROUND: Because it is not metabolized as is norepinephrine (NE), most of the metaiodobenzylguanidine (MIBG) taken up by the heart is considered to be lost subsequently by release concomitant with sympathetic stimulation. Therefore we examined whether the washout of MIBG is influenced by sympathetic tone, which we modulated by using immobilization stress or activation of the renin-angiotensin system (RAS). METHODS AND RESULTS: In 175 male ddY mice, left ventricular radioactivity was counted 30 minutes or 4 hours after injection of 74 kBq (2 microCi) of iodine 125- or iodine 131-labeled MIBG (125I- or 131I-MIBG). The washout rates of MIBG were determined under immobilization stress or under sodium loading or restriction in combination with losartan (10 mg/kg) or cilazapril (1 mg/kg) pretreatment. Immobilization enhanced the washout of 125I-MIBG (80.9% vs 57.9% in the control animals); this was determined to be related to washout from the neuronal compartment, because the nonneuronal component assessed through desipramine pretreatment was not affected. Pretreatment with losartan or cilazapril decreased the facilitation of 125I-MIBG washout in sodium-restricted mice (40.9% and 33.7%, respectively, vs 43.5% in the control animals), but not in sodium-loaded mice. CONCLUSIONS: Measurement of MIBG washout may be feasible for determining the changes in sympathetic tone caused by immobilization stress or activation of the RAS.     

123I-metaiodobenzylguanidine (MIBG) scintigraphy for the staging of neuroblastoma

Nineteen children with neuroblastoma (aged 2 w.-7 y.o.) were studied to evaluate the optimal scan conditions for Iodine-123-Metaiodobenzylguanidine (MIBG) scintigraphy for accurate staging at the time of diagnosis. Six and 24 hours after an injection of 123I-MIBG, whole body image and truncal spot and SPECT images were obtained. Compared with other studies (CT or MRI and bone scintigraphy), each 123I-MIBG image was evaluated visually to investigate which image can demonstrate the extent of neuroblastoma most exactly. MIBG images demonstrated primary tumors in all patients, and metastatic lymphadenopathy in 8 of 9 patients. Twenty-four hour SPECT images gave us the most detailed information about the extent of abnormal accumulation. As to bone and bone marrow lesions, 6 hour images were superior to 24 hour images in detectability. Moreover, MIBG showed many more lesions and more extended accumulation than the bone scan. 123I-MIBG scintigraphy was very useful in detecting neuroblastomas. In order to get the most valuable information, both delayed SPECT and early whole body planar images should be obtained.     

Iodine-131-metaiodobenzylguanidine dosimetry in cancer therapy: risk versus benefit

In the treatment of neural crest tumors, such as pheochromocytoma, with[131I]MIBG, bone marrow toxicity limits the amount of administered activity and, thus, a therapeutically useful tumor dose. METHODS: We calculated tumor doses in a series of diagnostic studies with [123I]MIBG using accurate quantification of SPECT and planar scintigraphy. By extrapolating diagnostic results to therapeutic activities of [131I]MIBG, we could compare the results with whole-body doses from a series of therapies. RESULTS: The tumor dose was DT = 2.2 mGy MBq(-1) (median value of 27 measurements, range 0.04 < or = DT < or = 20 mGy MBq(-1) and the whole-body dose in a series of 16 patients undergoing 50 therapies was DWB = 0.12 +/- 0.04 mGy MBq(-1) (mean +/- s.d.). The therapeutic ratio varied between 130 to below 10 in some patients. CONCLUSION: The results were compared with published data. We found clearly skewed distribution of tumor doses, with a majority of tumors receiving only a few mGy per MBq administered activity. In some patients, however, doses did reach 20 mGy MBq(-1).     

Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group

BACKGROUND: The unsatisfactory control of neuroendocrine tumor growth with chemotherapy and/or interferon (IFN-2a) stimulated us to investigate the role of the somatostatin analogue octreotide (SMS 201.995), which is reported to be highly effective in controlling carcinoid syndrome symptoms. Octreotide has been used in a wide range of doses, and it was postulated that higher doses might lead to an objective response. METHODS: The aim of the present multicenter Phase II study was to determine the safety and efficacy of SMS 201.995 in controlling carcinoids and other neuroendocrine tumors. Fifty-eight patients were treated subcutaneously with 2 sequential doses of the drug (Sandostatina, Sandoz, Inc., S.b.A. Pharmaceuticals, Basel, Switzerland). The first 23 patients received 500 micrograms 3 times a day and the remaining 35 patients received 1000 micrograms 3 times a day. The treatment was continued until the tumor progressed. RESULTS: All of the patients were adequately treated and evaluated. The predominant histotype was carcinoid, although there were instances of medullary thyroid carcinoma, pancreatic islet cell tumors, and Merkel cell carcinoma. Carcinoid syndrome was documented in 16 patients and abnormal urinary 5-hydroxyindoloacetic acid excretion in 15. The median treatment duration was 5 months (range, 2-31 months). The responses were evaluated in three categories: tumor regression for tumor growth control, symptom response, and biochemical response. There was an effect on tumor growth in two patients with carcinoids. Symptomatic control was achieved in 73% of patients and a biochemical response in 77% of patients. In twenty-seven patients, the disease stabilized for at least 6 months (range, 6-32+). The median survival time for all patients was 22 months (range, 1-32+). CONCLUSIONS: In terms of tumor regression, octreotide is disappointing (partial response: 3%); symptomatic response and biochemical control are satisfactory. These data confirm that somatostatin analogues are comparable to interferons in the treatment of carcinoid syndrome, although other efforts are necessary to control tumor regression.     

Occipital nerve neuralgia as postoperative complication. Views on etiology and treatment

INTRODUCTION: Meta-iodobenzylguanidine (MIBG) in its 131I-labeled form is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. This well established drug may have additional clinical applications as a radiosensitizer or hyperthermic agent, ie., MIBG reportedly inhibits mitochondrial respiration in vitro. The mechanism for MIBG inhibition of cellular oxygen consumption is uncertain. Moreover, MIBG reportedly stimulates glycolysis both in vitro and in vivo. Our studies show the effect of MIBG on 9L glioma oxygen consumption and redox status with tumors cells in vitro and in vivo. MATERIALS AND METHODS: The effects on electron transfer were determined by following oxygen consumption with a Clark oxygen electrode. Fluorescence measurements were used to determine effects of MIBG on intracellular electron acceptors, NADPH and flavoproteins, in vitro and in vivo. 31P-NMR was used to determine alterations in tumor cell pH in vivo. RESULTS: Our results show the inhibition of oxygen utilization with MIBG for cell suspensions in vitro. The same results were demonstrated for tumor cell suspensions rapidly isolated from tumors grown in rats. Moreover, NAD(P)H and flavoprotein (Fp) fluorescence changes were observed to rapidly occur following MIBG addition in vitro. Changes in intracellular pH measured with 31P-NMR, in vivo, precede the changes in fluorescence of NAD(P)H and Fp obtained with frozen sections of tumor. CONCLUSIONS: We conclude that 31P-NMR measurements and fluorescence changes, following MIBG injection, can be used as criterion for selecting the proper time to treat tumors with ionizing radiation or hyperthermia.     

Clinical relevance of I-123/I-131-MIBG scintigraphy in intestinal carcinoid tumors

AIM: Of this retrospective study was to determine the value of MIBG-scintigraphy in patients with intestinal carcinoids dependent on histological, clinical, and biochemical parameters. METHODS: In 15 patients uptake in carcinoid tumors and metastasis was correlated with location of the primary tumor, intra- and extrahepatic tumor masses, histology, immunhistochemistry, neuroendocrinological markers, and clinical symptoms. RESULTS: High uptake was to be seen almost only in tumor masses of primary tumors located in the terminal ileum. There also was a positive correlation with clinical symptoms for carcinoids and urinary 5-HIAA level. No correlation between MIBG uptake and tumor masses, histology, and most of the immunhistochemical and neuroendocrinological markers could be found. CONCLUSION: There is a limited indication for MIBG-scintigraphy in follow up of intestinal carcinoids. In patient with proven uptake MIBG scintigraphy is suitable for long-term follow up and therapy monitoring.     

Scientific challenges in environmental carcinogenesis

Myocardial uptake of iodine-123 meta-iodobenzylguanidine (123I-MIBG) was measured using scintigrams at rest in 12 patients with isolated, nonischemic mitral regurgitation (MR; regurgitant fraction 64% +/- 7%) and was related to the left ventricular (LV) function assessed by cardiac catheterization. Iodine-123 meta-iodobenzylguanidine activity in the upper mediastinum, liver, and lung was comparable between MR and control (n = 8) patients. The heart-to-mediastinum 123I-MIBG activity ratio 4 hours after injection was significantly (p < 0.01) decreased in MR (2.0 +/- 0.1, mean +/- SE) compared with control (2.7 +/- 0.1) with the increased clearance of MIBG. In addition, MR patients had significantly greater heterogeneity in the 123I-MIBG distribution within the myocardial images (26.1% +/- 2.1% intraimage variability for MR versus 15.6% +/- 0.8% for control, p < 0.01). Myocardial 123I-MIBG activity correlated positively with cardiac index and negatively with pulmonary capillary wedge pressure and LV volume indexes. Thus, 123I-MIBG scintigrams can be a noninvasive method for assessing the contractile dysfunction in MR.     

Prospective randomized trial of chemoembolization versus intra-arterial injection of 131I-labeled-iodized oil in the treatment of hepatocellular carcinoma

Intra-arterial injection of radioactive Lipiodol has shown promising results in patients with hepatocellular carcinoma (HCC) and portal obstruction. The aim of this prospective, randomized trial was to compare the efficacy and tolerance of 131I-labeled Lipiodol and chemoembolization for the treatment of patients with HCC. From September 1990 to September 1993, 142 patients (135 men, 7 women; age: 65 +/- 6.6 years) were randomly assigned to treatment groups and given either intra-arterial injections of 131I-labeled Lipiodol (60 mCi; 2.2 GBq) (n = 73) or chemoembolization (70 mg cisplatin) (n = 69). Subsequent injections were given at 2, 5, 8, 12, and 18 months. Tumor response was assessed on the basis of tumor size and serum alpha-fetoprotein levels. Patient tolerance was assessed clinically and angiographically. Survival rate was the main end-point. A total of 129 patients (65 in the 131I-labeled Lipiodol group and 64 in the chemoembolization group) were available for analysis; 13 were excluded, mainly because of portal vein thrombosis. The two groups were comparable. Actuarial survival curves were not significantly different between the two groups. Overall survival rates at 6 months, 1, 2, 3, and 4 years were 69%, 38%, 22%, 14%, and 10%, and 66%, 42%, 22%, 3%, and 0% in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Reduction in tumor size was similar for the two groups, with complete response in 1 and 0 patients and partial response in 15 and 16 patients in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Tolerance was significantly better in the 131I-labeled Lipiodol group both clinically (3 severe side effects vs. 29 in the chemoembolization group; P < .001) and angiographically (1 arterial thrombosis vs. 10 in the chemoembolization group; P < .01). In terms of patient survival and tumor response, radioactive 131I-labeled Lipiodol and chemoembolization were equally effective in the treatment of HCC, but tolerance to 131I-labeled Lipiodol was significantly better.     

Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions

Radiolabelled meta-iodobenzylguanidine (MIBG) is selectively taken up by tumours of neuroendocrine origin, where its cellular localization is believed to be cytoplasmic. The radiopharmaceutical [131I]MIBG is now widely used in the treatment of neuroblastoma, but other radioconjugates of benzylguanidine have been little studied. We have investigated the cytotoxic efficacy of beta, alpha and Auger electron-emitting radioconjugates in treating neuroblastoma cells grown in monolayer or spheroid culture. Using a no-carrier-added synthesis route, we produced 123I-, 125I-, 131I- and 211At-labelled benzylguanidines and compared their in vitro toxicity to the neuroblastoma cell line SK-N-BE(2c) grown in monolayer and spheroid culture. The Auger electron-emitting conjugates ([123I]MIBG and [125I]MIBG) and the alpha-emitting conjugate ([211At]MABG) were highly toxic to monolayers and small spheroids, whereas the beta-emitting conjugate [131I]MIBG was relatively ineffective. The Auger emitters were more effective than expected if the cellular localization of MIBG is cytoplasmic. As dosimetrically predicted however, [211At]MABG was found to be extremely potent in terms of both concentration of radioactivity and number of atoms ml(-1) administered. In contrast, the Auger electron emitters were ineffective in the treatment of larger spheroids, while the beta emitter showed greater efficacy. These findings suggest that short-range emitters would be well suited to the treatment of circulating tumour cells or small clumps, whereas beta emitters would be superior in the treatment of subclinical metastases or macroscopic tumours. These experimental results provide support for a clinical strategy of combinations ('cocktails') of radioconjugates in targeted radiotherapy.     

No-carrier-added synthesis of meta-[131I]iodobenzylguanidine

No-carrier-added meta-[131I]iodobenzylguanidine ([131I]MIBG) was prepared starting with two different metallated precursors. Attempted preparation of 3-(tri-n-butylstannyl)benzylguanidine was not successful. An alternate two-step strategy using 3-(tri-n-butylstannyl)benzylamine could be used to prepare radio-iodinated [131I]MIBG in an overall radiochemical yield of 30-33%. Synthesis of [131I]MIBG via the radioiododesilylation of 3-trimethylsilylbenzylguanidine was also investigated. Yields were dependent on temperature, precursor concentration, solvent and nature of the oxidant. Radiochemical yields of 90% were obtained in 5 min at room temperature using either N-chlorosuccinimide or hydrogen peroxide in trifluoroacetic acid as oxidants. The percentage of specific binding in vitro of no-carrier-added MIBG to SK-N-SH neuroblastoma cells remained constant over a 2 log activity range, while the binding of MIBG prepared by isotopic exchange dropped by a factor of seven. In normal mice, heart and adrenal uptake of no-carrier-added [131I]MIBG was found to be higher than that of [131I]MIBG prepared by isotopic exchange.     

Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma

PURPOSE: The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy. PATIENTS AND METHODS: Patients were first given tracelabeled doses of 131I-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose (15 to 20 mg) labeled with a quantity of 131I that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by an infusion of 135 mg of unlabeled anti-B1 one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1. RESULTS: Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment. CONCLUSION: Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.     

Managed care and outcomes of hospitalization among elderly patients with congestive heart failure

123I-radiolabeled metaiodobenzylguanidine (123I-MIBG) cardiac imaging has been used to evaluate the distribution of sympathetic nervous system (SNS) in the heart. Different heart diseases have shown impaired cardiac SNS distribution as reflected by MIBG activity. The aim of this study was to assess the cardiac distribution of SNS in normal subjects, using MIBG imaging. Ten normal subjects (1 male and 9 females, mean age 46 +/- 9 years) with no cardiac abnormalities underwent myocardial 123I-MIBG scintigraphy, Tc-99m methoxyisobutylisonitrile (MIBI) cardiac perfusion imaging and equilibrium radionuclide angiography (RNA). Regional myocardial MIBG and MIBI activities were quantitatively evaluated using a region of interest analysis. For this purpose, the left ventricle was divided into 6 myocardial regions as anterior, apical, inferior, septum, lateral and posterolateral. In particular, myocardial MIBG and MIBI activities were measured as myocardium to mediastinum ratio. Regional left ventricular function was assessed by RNA. Myocardial MIBG uptake was homogeneous in anterior (2.2 +/- 0.5), inferior (2.5 +/- 0.7), septal (2.4 +/- 0.4), lateral (2.3 +/- 0.4), and posterolateral (2.3 +/- 0.4) regions. Conversely, MIBG uptake was significantly lower in the apical region (1.9 +/- 0.3) compared to all other left ventricular segments (p < 0.05). Regional myocardial perfusion, as measured by MIBI uptake, was homogeneous in all regions. No regional left ventricular wall motion abnormalities were observed by RNA. In conclusion, our data suggest that a decreased MIBG uptake may be observed in the left ventricular apical region of normal subjects reflecting reduced sympathetic innervation of the apex. This finding is not related to myocardial perfusion or wall motion abnormalities. The knowledge of cardiac sympathetic innervation in normal subjects may be helpful to assess SNS abnormalities in heart disease.     

Diagnosis, radioiodine and radiotherapy of thyroid carcinomas

The long-term prognosis of differentiated thyroid carcinoma depends on early diagnosis and treatment of metastases and local recurrences and is modulated by several factors, age and histology being the most relevant. This article summarizes current trends in the use of radioactive iodine (131J) and gives explicit advice on its use in the treatment of these cancers. Complications of therapy are discussed in detail. We currently recommend that all patients undergoing a subtotal or total thyroidectomy are followed up by 131J thyroid scanning approximately 4 weeks after surgery. The combined use of three diagnostic modalities (measurement of serum thyroglobulin, neck ultrasonography with ultrasound-guided biopsy for detecting recurrences of carcinoma in the neck region and 131J whole-body scintigraphy) appears to give the best results in the follow up of patients with differentiated thyroid carcinoma. If any residual uptake is detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation with 1,5-3 GBq of radioactive 131J. External radiotherapy is always indicated in papillary and folliculary carcinoma in the pT4 stage of pTNM classification but not in those in pT1-3 pN0 stage. In the presence of lymph-node metastases and distant metastases, an individual treatment concept is recommended regarding all risk factors, especially the age and sex of the patient, the histology and grading of the tumor and the completeness of tumor resection. Finally, radiotherapy is usually not indicated in medullary carcinoma, whereas it is always indicated in anaplastic carcinoma.