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Maimoun L.,Service dHormonologie | Coste O.,Service dHormonologie | Jaussent A.,Departement de lInformation Medicale | Mariano-Goulart D.,Service de Medecine Nucleaire | And 2 more authors.
Clinical Endocrinology | Year: 2010

Objectives Although hypoleptinaemia has been reported in female peripubertal athletes, data are lacking on leptin and bone mass variations in puberty and the effects of leptin on bone mineralization during this period. This study therefore investigated the variations in leptin level and bone mineral density (BMD) in young elite female rhythmic gymnasts (FRG) according to pubertal stage. The effects of leptin, IGF-1 and sex hormones on bone mineral acquisition were also evaluated. Patients and measurements Plasma leptin levels were analysed in 43 elite FRG (mean age: 13·3 ± 1·8 years range: 10·6-17·2, body mass index: 17·52 ± 1·85 kg/m, training status: 17·9-23·8 h/week) according to their pubertal stage (Tanner I, n = 7; II, n = 10; III, n = 9; IV, n = 8; V, n = 9). IGF-1, IGFBP-3 and sex hormones were also evaluated. BMD was measured by dual-energy X-ray absorptiometry at various bone sites. Results Plasma leptin increased throughout pubertal growth and the values measured in Tanner stages IV-V were significantly higher than in stages I-II. Gains in BMD were measured throughout puberty at all bone sites, particularly between Tanner stages II and IV. In simple correlation analysis, BMD at all bone sites was positively correlated with plasma leptin, age, bone age, BMI, oestrogen, testosterone, IGF-1 and IGFBP-3. However, multivariate analysis using a linear regression model by block (including bone age, anthropometric data and biological parameters) was then performed to determine the factors independently associated with each BMD site, and only bone age, fat-free soft tissue and BMI remained independent predictors. Conclusion In FRG characterized by high training volume and low fat mass, plasma leptin levels increased throughout puberty and were partially related to body composition changes. Despite the simultaneous increases in plasma leptin and BMD during pubertal growth, it was not possible to differentiate the leptin impact on bone independently from anthropometric parameters. © 2010 Blackwell Publishing Ltd.


Matthay K.K.,University of California at San Francisco | Shulkin B.,St Jude Childrens Research Hospital | Michon J.,University Pierre and Marie Curie | Giammarile F.,Service de Medecine Nucleaire | And 3 more authors.
British Journal of Cancer | Year: 2010

Background:Neuroblastoma is an embryonic tumour of the sympathetic nervous system, metastatic in half of the patients at diagnosis, with a high preponderance of osteomedullary disease, making accurate evaluation of metastatic sites and response to therapy challenging. Metaiodobenzylguanidine (mIBG), taken into cells via the norepinephrine transporter, provides a sensitive and specific method of assessing tumour in both soft tissue and bone sites. The goal of this report was to develop consensus guidelines for the use of mIBG scans in staging, response assessment and surveillance in neuroblastoma.Methods:The International Neuroblastoma Risk Group (INRG) Task Force, including a multidisciplinary group in paediatric oncology of North and South America, Europe, Oceania and Asia, formed a subcommittee on metastatic disease evaluation, including expert nuclear medicine physicians and oncologists, who developed these guidelines based on their experience and the medical literature, with approval by the larger INRG Task Force.Results: Guidelines for patient preparation, radiotracer administration, techniques of scanning including timing, energy, specific views, and use of single photon emission computed tomography are included. Optimal timing of scans in relation to therapy and for surveillance is reviewed. Validated semi-quantitative scoring methods in current use are reviewed, with recommendations for use in prognosis and response evaluation.Conclusions:Metaiodobenzylguanidine scans are the most sensitive and specific method of staging and response evaluation in neuroblastoma, particularly when used with a semi-quantitative scoring method. Use of the optimal techniques for mIBG in staging and response, including a semi-quantitative score, is essential for evaluation of the efficacy of new therapy. © 2010 Cancer Research UK All rights reserved.


Pastor C.M.,Laboratoire Of Physiopathologie Hepatique Et Imagerie Moleculaire | Wissmeyer M.,Service de Medecine Nucleaire | Millet P.,Unite Of Neurophysiologie Clinique Et Neuroimagerie Hopitaux Universitaires Of Geneva
Contrast Media and Molecular Imaging | Year: 2013

Gd-BOPTA (gadobenate dimeglumine) is a magnetic resonance (MR) contrast agent that, after i.v. administration, distributes within the extracellular space, enters rat hepatocytes through the sinusoidal transporters organic anion transporting peptides (Oatps) and is excreted unchanged into bile through the multidrug resistance-associated protein 2 (Mrp2). It is unclear how the hepatobiliary contrast agent would accumulate in cholestatic fatty livers from obese rats with bile flow impairment. Indeed, the expression of both Oatps and Mrp2 transporters is decreased in cholestatic hepatocytes. To assess this question, we measured on-line the hepatic concentrations of 153Gd-BOPTA with a gamma probe placed over perfused rat livers. During the perfusion of 153Gd-BOPTA, we obtained a similar maximal hepatic concentration in normal and fatty livers despite the decreased expression and function of membrane transporters in fatty livers. By pharmacokinetic modeling and mathematical simulations, we show how changes of transport into and out of hepatocytes modify the concentrations of 153Gd-BOPTA within hepatocytes. Mathematical simulations help to understand how each parameter (entry into hepatocytes, bile excretion, or efflux back to sinusoids) interferes with the hepatic concentrations. The hepatic concentrations of 153Gd-BOPTA within hepatocytes rely on the entry into hepatocytes through the sinusoidal membrane and on two paths of exit, the efflux back to sinusoids and the elimination into bile. Understanding how 153Gd-BOPTA accumulates in hepatocytes is then complex. However, such understanding is important to analyze liver imaging with hepatobiliary contrast agents in cholestatic fatty livers. © 2012 John Wiley & Sons, Ltd.


Trotman J.,University of Sydney | Luminari S.,University of Modena and Reggio Emilia | Boussetta S.,Center Hospitalier Lyon Sud | Versari A.,Santa Maria Nuova Hospital | And 14 more authors.
The Lancet Haematology | Year: 2014

Background: The value of 18F-fl uorodeoxyglucose (FDG) PET-CT (PET) imaging in response assessment after fi rst-line rituximab chemotherapy for follicular lymphoma has been documented. We analysed the application of the fi ve-point Deauville scale (5PS; used to score FDG uptake on PET images) in a large cohort derived from three studies, to assess the correlation between post-induction PET status and survival in patients with follicular lymphoma. Methods: In this pooled analysis, we used data from three multicentre prospective studies of fi rst-line rituximab chemotherapy for patients with high-tumour-burden follicular lymphoma (the PRIMA study, the PET-Folliculaire study, and the Fondazione Italiana Linfomi FOLL05 study). Patients included in this analysis received at least six cycles of rituximab and chemotherapy before response assessment with conventional contrast-enhanced CT and PET low-dose CT (PET). We included only patients who had a PET scan within 3 months of the last dose of induction rituximab. Patient data, including conventional CT-based response assessment, were recorded for all patients undergoing PET review. Scans undergoing central PET review were scored independently by three reviewers according to the 5PS. The primary endpoints were progression-free survival and overall survival according to the 5PS score of post-induction PET scan (ie, positive [≥4 points] or negative [<4 points]), analysed in the central review population. Findings: Between Dec 24, 2004, and Sept 22, 2010, 439 of the patients enrolled in the three studies underwent local PET assessment, 246 of whom had centrally reviewed post-induction scans. 41 (17%) of 246 patients had a positive post-induction PET scan according to a cutoff of 4 or higher on the 5PS, with substantial reporter concordance. With a median follow-up of 54.8 months (IQR 39.7-68.5; range 7.7-90.1), the hazard ratio (HR) for progression-free survival for patients with a positive PET scan versus those with a negative PET scan was 3.9 (95% CI 2.5-5.9; p<0.0001), and for overall survival was 6.7 (2.4-18.5; p=0.0002). For patients with a positive PET scan, 23.2% (95% CI 11.1-37.9) of patients were progression free at 4 years compared with 63.4% (55.9-70.0) of those who had a negative PET scan (p<0.0001); 4-year overall survival was 87.2% (95% CI 71.9-94.5) versus 97.1% (93.2-98.8), respectively (p<0.0001). Conventional CT-based response (ie, complete response or unconfi rmed complete response vs partial response) was weakly predictive of progression-free survival (HR 1.7 [95% CI 1.1-2.5]; p=0.017). Interpretation: PET-CT rather than contrast-enhanced CT scanning should be considered as a new standard for response assessment of follicular lymphoma in clinical practice, and could help guide response-adapted therapy. Funding: Groupe d'Etude des Lymphomes de l'Adulte (Paris, France), now LYSA (Lymphoma Study Association), Direction de la Recherche Clinique de l'Assistance Publique-Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health.


Hassler S.,Service de Medecine Nucleaire | Ben-Sellem D.,Institute Salah Azaiez | Hubele F.,Hopitaux Universitaires Of Strasbourg | Constantinesco A.,Hopitaux Universitaires Of Strasbourg | Goetz C.,Hopitaux Universitaires Of Strasbourg
Clinical Nuclear Medicine | Year: 2014

PURPOSE: In patients with primary hyperparathyroidism, the preoperative imaging objective is to locate accurately and reliably uniglandular or multiglandular hyperfunctioning parathyroid, to guide surgery, particularly for minimally invasive method. Subtraction planar scintigraphy with dual-isotope (123I/99mTc-MIBI) is an efficient examination to specify abnormal parathyroid location, but without accurate anatomic reference. This lack should be avoided by a hybrid SPECT/CT image acquisition. METHODS: We compared planar scans (neck and mediastinum parallel-hole, associated with anterior neck pinhole) to neck and mediastinum SPECT/CT, all with subtraction (123I/99mTc-MIBI) method, in exact location of abnormal parathyroid in 50 patients with sporadic primary hyperparathyroidism. Surgical and histological findings were used as the standard of comparison. RESULTS: Sensitivity is equivalent for the 2 protocols (86% and 75% for SPECT/CT and planar protocol, respectively, P = 0.15), but SPECT/CT was highly specific (specificity 100% and 90% for SPECT/CT and planar protocol, respectively, P = 0.04). In patients with concomitant thyroid disease, subtraction SPECT/CT appeared to be more sensitive than planar protocol (88% and 62% for SPECT/CT and planar protocol, respectively, P = 0.04). CONCLUSIONS: In preoperative assessment of primary hyperparathyroidism and to guide surgery, we propose to perform first subtraction SPECT/CT and to complete it with neck pinhole, only if tomoscintigraphy is negative. Copyright © 2013 by Lippincott Williams & Wilkins.


Nunes H.,Service de Pneumologie | Freynet O.,Service de Pneumologie | Naggara N.,Service de Radiologie | Soussan M.,Service de Medecine Nucleaire | And 4 more authors.
Seminars in Respiratory and Critical Care Medicine | Year: 2010

Cardiac involvement is undeniably one of the most challenging issues in sarcoidosis. Although autopsy studies reveal heart lesions in 20 to 30% of sarcoid patients, fewer than 5% suffer from clinical disease. Cardiac sarcoidosis (CS) has a predilection for the myocardium, but the pericardium and endocardium may also be affected. CS manifestations are various and most frequently include the following: (1) aberrations of atrioventricular or intraventricular conduction, either silent or symptomatic; (2) ventricular arrhythmias; (3) subacute congestive heart failure; and (4) sudden death. CS must be detected in all sarcoid patients by means of detailed medical history, physical examination, and resting electrocardiogram (ECG) at first evaluation and during follow-up. In patients with suspected CS, further investigations are aimed at evaluating diagnosis and cardiac consequences. Unfortunately, no gold standard exists that would allow CS diagnosis with a level of confidence. Endomyocardial biopsy is an invasive procedure that lacks sensitivity. Patients need, at a minimum, specialized cardiologic advice, echocardiography, and 24-hour ambulatory ECG. Other diagnostic tools include thallium, technetium, and gallium scintigraphy, and more recently, 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance (CMR). The respective role of these new imaging tools in the diagnostic approach remains to be defined. CMR has the advantage of not exposing patients to radiation, but it is not feasible in those with cardiac devices. In Western countries, heart involvement accounts for 13 to 25% of sarcoidosis-related deaths, and it is the leading cause of mortality in Japan. The main prognostic indicators are New York Heart Association functional class, left ventricular enlargement, and sustained ventricular tachycardia. Treatment is based on systemic corticosteroids with an initial dose between 30 mg/day and 1 mg/kg/day (which is usually maintained for at least 24 months), specific cardiologic agents, and the placement of a pacemaker or implantable cardiac defibrillator in case of an atrioventricular block or severe intractable ventricular arrhythmias. Cardiac transplantation is exceptionally required. Copyright © 2010 by Thieme Medical Publishers, Inc.


The role of FDG-PET/CT in lymphoma is described in the various lymphoma subtypes. Its prognostic value and comparison with CECT are addressed in this review. © 2011 Springer Verlag France.


Arnoux J.-B.,University of Paris Descartes | Verkarre V.,AP HP Hopital Necker Enfants Malades | Saint-Martin C.,University Pierre and Marie Curie | Montravers F.,Service de Medecine Nucleaire | And 8 more authors.
Orphanet Journal of Rare Diseases | Year: 2011

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic -cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable. © 2011 Arnoux et al; licensee BioMed Central Ltd.


Champion L.,Service de Medecine Nucleaire | Lerebours F.,Service dOncologie Medicale | Cherel P.,Institute Curie | Edeline V.,Service de Medecine Nucleaire | And 6 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2013

Purpose: Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer with a poor prognosis. Locoregional staging is based on dynamic contrast-enhanced (DCE) CT or MRI. The aim of this study was to compare the performances of FDG PET/CT and DCE CT in locoregional staging of IBC and to assess their respective prognostic values. Methods: The study group comprised 50 women (median age: 51 ± 11 years) followed in our institution for IBC who underwent FDG PET/CT and DCE CT scans (median interval 5 ± 9 days). CT enhancement parameters were net maximal enhancement, net early enhancement and perfusion. Results: The PET/CT scans showed intense FDG uptake in all primary tumours. Concordance rate between PET/CT and DCE CT for breast tumour localization was 92 %. No significant correlation was found between SUVmax and CT enhancement parameters in primary tumours (p > 0.6). PET/CT and DCE CT results were poorly correlated for skin infiltration (kappa = 0.19). Ipsilateral foci of increased axillary FDG uptake were found in 47 patients (median SUV: 7.9 ± 5.4), whereas enlarged axillary lymph nodes were observed on DCE CT in 43 patients. Results for axillary node involvement were fairly well correlated (kappa = 0.55). Nineteen patients (38 %) were found to be metastatic on PET/CT scan with a significant shorter progression-free survival than patients without distant lesions (p = 0.01). In the primary tumour, no statistically significant difference was observed between high and moderate tumour FDG uptake on survival, using an SUVmax cut-off of 5 (p = 0.7 and 0.9), or between high and low tumour enhancement on DCE CT (p > 0.8). Conclusion: FDG PET/CT imaging provided additional information concerning locoregional involvement to that provided by DCE CT on and allowed detection of distant metastases in the same whole-body procedure. Tumour FDG uptake or CT enhancement parameters were not correlated and were not found to have any prognostic value. © 2013 Springer-Verlag Berlin Heidelberg.


Champion L.,Institute Curie | Brain E.,Institute Curie | Giraudet A.-L.,Institute Curie | Le Stanc E.,Service de Medecine Nucleaire | And 8 more authors.
Cancer | Year: 2011

Background: Breast cancer recurrence is often suspected on tumor marker rising in asymptomatic patients. The value of fluorine-18 fluorodeoxyglucose (18FDG)-positron emission tomography/computed tomography (PET/CT) imaging to detect recurrence and its subsequent impact on patient management were retrospectively assessed. Methods: PET/CT scans were performed on 228 asymptomatic patients (mean, 60.8 years; range, 30-91 years) presenting with rising CA 15-3 and/or CEA serum levels. Results: PET/CT scans were positive in 181 patients (79.5%) and normal in 47 patients, whereas 187 true recurrences were diagnosed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT imaging for detection of breast cancer recurrence were 93.6%, 85.4%, 96.7%, 74.5%, and 92.1%, respectively. When compared with the standard workup available in 67 patients, PET/CT imaging had a higher sensitivity and accuracy (94.5% vs 33% and 94% vs 48%, respectively). Recurrences were confirmed by pathology, conventional imaging techniques, or radiological and clinical follow-up beyond 1 year (mean, 34 months; range, 12-67 years) in 32, 130, and 25 patients, respectively. The diagnosis of recurrence led to a treatment modification in 123 patients (54%). Conclusions: 18FDG-PET/CT imaging is an efficient technique to detect breast cancer recurrence suspected on tumor marker rising in asymptomatic patients. It may thus contribute to improve patient management, providing an earlier diagnosis with complete whole-body staging as a "one-stop shop" procedure. © 2010 American Cancer Society.

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