non-maleficence by integrating the diagnostic results into the broader psychosocial and medical management context of patient care under the continuing care of another clinician.This distinction has been increasingly blurred also in the context of theranostics wherein the nuclear medicine specialist is actively involved in management decisions and delivering therapy based on imaging results.Another important consideration is the training of those involved in nuclear medicine.In some countries, nuclear medicine scan interpretation is performed primarily by radiologists with little or no training in internal medicine whereas in other countries, like France, physician training and experience in patient management are more common.Recognising the specific circumstances that exist in France, we conducted a survey in 2015 that focused on the daily practices of nuclear medicine physicians in delivery of PET findings to cancers patients [1,2].This study uncovered significant diversity in practices with 63% of physicians stating they disclosed results on a case-by-case basis and only 13% doing so routinely, while the remaining participants never disclosed imaging findings.The vast majority of physicians emphasized the absence of specific guidelines regarding how practitioners should inform patients of nuclear medicine results.Accordingly, in 2017, a multidisciplinary ethics group was formed under the umbrella of the French Society of Nuclear Medicine to establish an ethical charter, which wasapproved by the national society in 2019 and sent to all French nuclear medicine departments with encouragement to adopt and prominently exhibit it.The ethical charter encompasses seven essential points, and states that every patient undergoing imaging examination should be provided an opportunity to meet with a nuclear medicine physician to receive clear, honest, and tailored information, taking into account their level of medical literacy.This discussion should ideally take place in a dedicated space to guarantee privacy and psychological security.The ultimate

Background No reliable biomarkers are identified in KLS. However, few functional neuroimaging studies suggested hypoactivity in thalamic and hypothalamic regions during symptomatic episodes. Here, we investigated relative changes in regional brain metabolism in Kleine-Levin syndrome (KLS) during symptomatic episodes and asymptomatic periods, as compared to healthy controls. Methods Four drug-free male patients with typical KLS and 15 healthy controls were included. 18-F-fluorodeoxy glucose positron emission tomography (PET) was obtained in baseline condition in all participants, and during symptomatic episodes in KLS patients. All participants were asked to remain fully awake during the whole PET procedure. Results Between state-comparisons in KLS disclosed higher metabolism in paracentral, precentral, and postcentral areas, supplementary motor area, medial frontal gyrus, thalamus and putamen during symptomatic episodes, and decreased metabolism in occipital and temporal gyri. As compared to healthy control subjects, KLS patients in the asymptomatic phase consistently exhibited significant hypermetabolism in a wide cortical network including frontal and temporal cortices, posterior cingulate and precuneus, with no detected hypometabolism. In symptomatic KLS episodes, hypermetabolism was additionally found in orbital frontal and supplementary motor areas, insula and inferior parietal areas, and right caudate nucleus, and hypometabolism in the middle occipital gyrus and inferior parietal areas. Conclusion Our results demonstrated significant hypermetabolism and few hypometabolism in specific but widespread brain regions in drug-free KLS patients at baseline and during symptomatic episodes, highlighting the behavioral state-dependent nature of changes in regional brain activity in KLS.

OBJECTIVE:To investigate brain changes in both basal and cataplectic conditions in awake patients with narcolepsy-cataplexy.BACKGROUND:Recent insights in pathophysiology have demonstrated that narcolepsy-cataplexy is caused by early loss of hypothalamus hypocretin neurons. However, the neurophysiological mechanisms underlying sleepiness and the dramatic cataplexy reaction to positive emotion remain unclear.METHODS:Twenty-one patients with narcolepsy-cataplexy and 21 age- and sex-matched controls were included. Diagnosis of narcolepsy was fully confirmed by polysomnography, HLA DQB1*0602 and CSF hypocretin levels (n=9). Seven patients were free of all drugs, and 14 were treated with psychostimulant and/or anticataplectic drugs. (18)-F-fluorodeoxy glucose positron emission tomography procedures were performed at baseline in all subjects and during cataplexy attacks (n=2).RESULTS:The authors found significant hypermetabolism in narcolepsy-cataplexy in fully awake condition in the limbic cortex specifically in the anterior and mid cingulate cortex, in the right cuneus and lingual gyrus. In contrast, no hypometabolism was found. Hypermetabolism was detected in the cerebellum and pre-postcentral gyri in treated compared with untreated patients. During cataplectic attacks, cerebral metabolism significantly increased in the bilateral pre-postcentral gyri, primary somatosensory cortex, with a marked decrease in the hypothalamus.CONCLUSION:Hypermetabolism was found in the executive network in narcolepsy at baseline in fully awake condition. Wake state assessment during scanning appears critical to avoid results showing altered functional neurocircuitry secondary to sleepiness and not to the underlying neurological disorder per se. Finally, cataplexy attacks were characterised by a hypometabolism in the hypothalamus associated with wide bilateral brain area hypermetabolisms.

We prospectively investigated the use of [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) to kinetically monitor cell activation in six follicular lymphoma patients vaccinated with tumor lysate-pulsed autologous dendritic cells. PET revealed additional initial nodes suggestive of lymphoma, that were of less than 10 mm of diameter on computed tomography, and documented disease progression with sensitivity, even within loci with no significant variations of CT findings. Although tracer fixation was not observed in the inguinal nodes draining the dendritic cell intradermal injection sites in the six patients, a transient marked increase in FDG uptake within malignant nodes was observed early after vaccine administration in a patient who achieved complete remission. In non-responding patients, we observed a continuous increase of FDG uptake associated with an increase in the size and number of pathological nodes/locus, or of involved loci. FDG-PET is a non-invasive imaging procedure that might be of crucial interest to detect cell responses induced by immunotherapies.

Except in the subset of patients with localized disease, follicular lymphoma (FL), the most common type of indolent non-Hodgkin's lymphoma, should still be regarded as an incurable malignancy with a relentless relapsing course. New therapeutic approaches have been developed including anti-tumor vaccination strategies with induced humoral and cellular immune responses revealed by sensitive biological analyses but no imaging of the lymphocyte activation developed so far. Because [18F]fluorodeoxyglucose (FDG) is sequestred in metabolically active cells, we prospectively investigated the use of FDG-PET (positron emission tomography) to kinetically monitor cell activation in 7 FL patients vaccinated by repeated intradermal (ID) and intravenous injections of tumor lysate-pulsed autologous dendritic cells (DC-lysate). Patients were administered 5 vaccines and all patients developed a positive delayed-type hypersensitivity reaction at the site of DC-lysate ID injections after several vaccines administration, testifying of the induction of a biological response. Among the 4 patients with measurable disease at time of vaccination, 2 complete remissions (CR) and 2 disease progressions were observed. Three patients with initial normal computed tomographies (CT) were still in CR 12 months after the last vaccine. PETs were performed before vaccination, 14 days and 1 month after the last vaccine. PET revealed initial malignant nodes infracentimetric on concomitant CT, and was very sensitive in documenting disease progression even in patients with no significant variations of CT findings. A transient marked increase in FDG uptake within malignant nodes was observed early after vaccine administration in a patient who achieved a CR (fig 1-3-4-5), while ranges of tracer uptake variations were less important with a continuous increase of FGD uptake, size and number of involved loci in non responding patients (fig 2: follow up of intensity of FDG uptake by 6 tumoral nodes in a non responding pt). In conclusion, FDG-PET is a non invasive imaging procedure which besides being useful for the staging and the evaluation of treatment efficacy in FL, might be of crucial interest to detect cell responses induced by immunotherapies.

We report the case of a 39-year-old woman with systemic lupus erythematosus (SLE), who was seen for excruciating rib pain, thrombocytopenia, anemia, renal failure, and an inflammatory syndrome. She was treated with high-dose steroids. A bone scan performed initially revealed upper thoracic cage photopenia and was suggestive of a vaso-occlusive crisis. At the same time, thrombophlebitis of the right arm was diagnosed. The presence of a lupus anticoagulant was highlighted. Plasmapheresis initiated 5 days after the bone scan relieved the patient immediately. A follow-up bone scan performed 20 days after the initial study showed improvement in uptake of the upper anterior ribs and confirmed the diagnosis of vaso-occlusive crisis.

Purpose: The main goal of sentinel lymph node (SLN) detection in head and neck squamous cell carcinomas is to limit neck dissections to pN+ cases only. However, intraoperative+diagnosis cannot be routinely done using the current gold standard, serial step sectioning with immunohistochemistry. Real-time quantitative reverse transcription-PCR (RT-PCR) is potentially compatible with intraoperative use, proving highly sensitive in detecting molecular markers. This study post-operatively assessed the accuracy of quantitative RT-PCR in staging patients from their SLN.Experimental Design: A combined analysis on the same SLN by serial step sectioning with immunohistochemistry and quantitative RT-PCR targeting cytokeratins 5, 14, and 17 was done in 18 consecutive patients with oral or oropharyngeal squamous cell carcinoma and 10 control subjects.Results: From 71 lymph nodes examined, m RNA levels (KRT) were linked to metastasis size for the three cytokeratins studied (Pearson correlation coefficient, r=0.89, 0.73, and 0.77 for KRT 5, 14, and 17 respectively; P<0.05). Histopathology-positive SLNs (macro- and micrometastases) showed higher mRNA values than negative SLNs for KRT 17 (p<10(-4)) and KRT 14 (p<10(-2)). KRT 5 showed nonsignificant results. KRT17 seemed to be the most accurate marker for the diagnosis of micrometastases of a size >450 mu m. Smaller micrometastases and isolated tumor cells did not provide results above the background level. Receiver operating characteristic curve analysis for KRT 17 identified a cutoff value where patient staging reached 100% specificity and sensitivity for macro- and micrometastases.Conclusion: Quantitative RT-PCR for SLN staging in cN(0) patients with oral and oropharyngeal squamous cell carcinoma seems to be a promising approach.

BackgroundThe management and prognosis of a glioma depend on the tumour's histological grade. Thus, preoperative prediction of the grade is routinely needed to indicate whether surgery or biopsies are required. It has been proposed that thallium single photon emission computed tomography (SPECT), in a relative short series, will aid this prediction. AimTo confirm the correlation between the results of preoperative thallium SPECT and grade of tumour as well as patient survival, and to define the cut-off value of the optimal thallium index for the detection of high grade gliomas in a large series of patients. MethodsOne hundred and eighteen patients treated for glioma were retrospectively included in this study. All patients underwent preoperative 201Tl SPECT upon initial presentation and were referred for neurosurgery. Initial scintigraphic findings were correlated with the histological grade of the tumour and overall patient survival. ResultsThallium uptake was highly correlated with histological grade; the mean thallium indices for low grade and high grade gliomas were 1.8 and 4.9, respectively. On the basis of receiver operating characteristic analysis, the optimal cut-off value of the thallium index for the detection of high grade glioma was determined. By using 2.2 as the value for the threshold thallium index, the sensitivity and specificity were 93% and 72%, respectively. Kaplan–Meier estimates of the overall survival curves, as a function of the thallium index, indicated that it was correlated with the overall survival (P<0.001). ConclusionThallium SPECT provides useful information about the histological grade of the tumour and overall patient survival. Additionally, in spite of its relatively weak resolution, it appears to be a powerful routine clinical tool for the management of gliomas.

Somatostatin receptor scintigraphy is habitually indicated in the evaluation of neuroendocrine tumors. We report the case of a 44-year-old woman with an unexpected vasculitis, which was detected on In-111 pentetreotide scintigraphy. Vascular uptake of the tracer was observed at presentation and disappeared after 3 months of corticotherapy.

DCs are the most potent antigen-presenting cells and antigen (Ag) delivery by ex vivo Ag-loaded DC cells may be an effective strategy for FL. The relevant source of tumor Ag, vaccine doses, schedules or routes of administration are still a matter of investigation. Tumor cell lysate (TCL) is an interesting source of multiple tumor Ag. After preclinical study and an acceptation of the “dossier de lot” by the french drug agency (afssaps), we started a phase II study evaluating the feasibility and safety of multiple ID and IV injections of autologous DC-TCL, in 07/04. At this time, 5 FL patients (pts) completed their treatment, with 5 to 7 DC-TCL vaccinations every 2–3 weeks, receiving 5.106 cells IV and 5.106 cells ID per vaccination. All the pts (2F/ 3M, age 44–61; 1 to 8 previous lines of therapy, including autologous transplantion in 2 pts) had measurable disease at inclusion. Tumor lymph node biopsy (for preparing TCL) was followed by rituximab administration in pts with no history of previous infusion of the monoclonal antibody. Cyclophosphamide (2g/m2) and G-CSF (5 mg/kg) were administered to mobilize mononuclear cells including CD14 monocytes. Two pts still had measurable disease at time of vaccination (lymph nodes on CT and Pet scans for the 2 pts, cutaneous localizations and molecular analysis evidence of disease in BM and PB, in 1 pt). Immature DC were obtained from thawed leukapheresis cells cultured for 5 days with GM-CSF and IL-4, pulsed with L, and then induced to mature with TNFalpha and PGE2 for 24 hours. All DC preparations fitted the quality criteria defined by the preclinical study (viability≥60%, ≤20% CD14+ cells, ≥60% CD83+ cells). Vaccinations were safe and well tolerated. One of the 2 pts with prevaccination residual disease entered CR (disappearance of Pet-scan positivity after the 7th vaccination, with sequential Pets, showing an increase of the signal during the first vaccinations linked to an initial lymph node activation), while a PR was observed in the 2nd pt with a regression of both lymph nodes and tumoral subcutaneous lesions. Quantitative PCR for bcl-2 signal were performed in both PB and BM. All pts developed significant delayed-type hypersensitivity responses to DC-TCL (as defined by erythema and induration of more than 5 mm of diameter, lasting 48h at least) after the 4th or 5th vaccinations. Analysis of biopsies performed at the site of DC-TCL injections, showed HSR including neutrophils and dense infiltration by T lymphocytes, mainly CD4 cells, as compared to site of injection of unmodified DC. Immunologic tests (Elispot assays) for monitoring vaccine efficacy will be presented. These preliminary results show that DC-TCL might be an efficient immunotherapy in patients with FL and that schedule of administration of the vaccine (especially to perform at least 5 vaccinations in a short period of time) as well as combination of 2 routes of DC administration might be critical points. We are now trying to pursue vaccinations for a longer period of time for every pt, and this study is now a multicenter study from Goelams group.

Background:Oropharyngeal and oral N0 squamous-cell carcinomas are upstaged to pN+ in nearly 35% of cases. Nevertheless, micrometastases can be missed by routine pathological examination. Sentinel lymph node (SLN) his- tology including immunohistochemistry may improve the sensitivity and specificity of node staging. The objec- tives of this study were to describe a technique for identifying and examining SLNs and to report preliminary results. Materials and method: Twenty consecutive patients were included prospectively. Lymphoscintigraphy was per- formed after injecting Nanocis® on D0. A handheld gamma probe was used for sentinel node identification during surgery. Sentinel nodes were examined by standard histology and immunohistochemistry. Neck dissection was per- formed routinely. Results: SLNs were identified in 19 patients. In the 4 patients with micrometastases, in-depth node studies led to pN upstaging from pN0 to pN2 in 1 patient and from pN1 to pN2 in 3 patients. No false negatives were recorded. Conclusion:The technique described in this study may improve node staging. A multicenter study is needed to confirm these preliminary findings and to evaluate outcomes according to node stage.

One of the major indications of tumor markers is the detection of occult disease. Less than 20 % of tumor markers elevations are associated with clinical or radiological findings. Such elevations have led medical community to doubt about the interest of markers follow-up, such as CA 15.3 in breast cancer. Now, positron emission tomography with (18)fluoro-desoxyglucose (18FDG-PET), using metabolic properties of malignant cells, is able to visualize tumor recurrences at an early stage of development, before any occurrence morphologic changes depicted by radiological examinations. Because of its cost and its limited accessibility, this functional technique should only be prescribed following a large set of informative indications, of which tumor markers belong. Early positive, non invasive and cost effectiveness, tumor markers become a precious guide in the prescription of 18FDG-PET in oncology. This article reviews the results of a set of recent studies in colorectal, breast and ovarian cancer.

We report a case of a 61-year-old man who underwent coronary artery bypass grafting in 1975 and progressively developed chronic sternal osteomyelitis. He was examined for fever with an increase of pain and swelling of the sternal scar. Computed tomographic scan performed 2 weeks before was normal. The patient was referred to the nuclear medicine department for a bone scan. There was a high level of blood-pool activity in the lower thorax in the blood-pool phase, and intense linear midline uptake was observed extending from the lower thorax into the upper abdomen in the late phase. Anterior and posterior Tc-99m HMPAO-labeled leukocyte images of the chest and abdomen obtained approximately 24 hours after injection demonstrated major accumulation in the same location extending to the anterior mediastinum. A control computed tomographic scan for comparison obtained 1 day later demonstrated a large retrosternal abscess with sternal osteomyelitis. This was confirmed at surgery with drainage of pus. Staphylococcus aureus was isolated. The patient was treated with appropriate antibiotics with good effect.

UNLABELLED:In about half of all patients with Legg-Calvé-Perthes disease (LCP), severe hip disorders that could be prevented by early surgery will develop. A prognostic test for this complication is also needed as part of routine care to help the surgeon manage LCD. The purpose of this study was to confirm the prognostic value of the bone scanning and pinhole imaging of the hip in LCP that Conway's group proposed in 1997 and to define accurate prognostic scintigraphic patterns.METHODS:Fifty-eight patients with LCP were recruited at initial presentation and followed for 1 y. Each patient underwent bone scanning initially and after 5, 8, and 12 mo of disease. The severity of the disease was assessed by radiography (the Catterall classification), MRI, and arthrography. Retrospectively, initial scintigraphic findings were correlated with severity.RESULTS:Among the 60 hips studied (2 patients had bilateral disease), severe hip disorders developed in 36. The positive predictive value of the scintigraphic classification proposed by Conway's group was 97% for the B pathway (absence of lateral column formation) and 85% for the A pathway (presence of lateral column formation). The hyperactivity of the metaphyseal growth plates was a sign of poor prognosis. The sensitivity was only 33%, but the positive predictive value was 92%. This prognostic information was obtained in as few as 5 mo after initial presentation.CONCLUSION:This study confirms the high prognostic value of bone scanning in LCP as reported by Conway's group not only in terms of the accuracy of the classification but also in terms of the short time in which the prognostic information can be obtained. Thus, we propose that bone scanning be used as part of routine care for the management of LCP.

The aim of this preliminary study was to evaluate the accuracy of left and right ventricular output computed from a semi-automatic processing of tomographic radionuclide ventriculography data (TRVG) in comparison with the conventional thermodilution method. Twenty patients with various heart diseases were prospectively included in the study. Thermodilution and TRVG acquisitions were carried out on the same day for all patients. Analysis of gated blood pool slices was performed using a watershed-based segmentation algorithm. Right and left ventricular output measured by TRVG correlated well with the measurements obtained with thermodilution (r = 0.94 and 0.91 with SEE = 0.38 and 0.46 l/min, respectively, P < 0.001). The limits of agreement for TRVG and thermodilution measurements were -0.78-1.20 l/min for the left ventricle and -0.34-1.16 l/min for the right ventricle. No significant difference was found between the results of TRVG and thermodilution with respect to left ventricular output (P = 0.09). A small but significant difference was found between right ventricular output measured by TRVG and both left ventricular output measured by TRVG (mean difference = 0.17 l/min, P = 0.04) and thermodilution-derived cardiac output (mean difference = 0.41 l/min, P = 0.0001). It is concluded that the watershed-based semi-automatic segmentation of TRVG slices provides non-invasive measurements of right and left ventricular output and stroke volumes at equilibrium, in routine clinical settings. Further studies are necessary to check whether the accuracy of these measurements is good enough to permit correct assessment of intracardiac shunts.

Background:Oropharyngeal and oral N0 squamous- cell carcinomas are upstaged to pN+ in nearly 35% of cases. Nevertheless, micrometastases can be missed by routine pathological examination. Sentinel lymph node (SLN) histology including immunohistochemis- try may improve the sensitivity and specificity of node staging. The objectives of this study were to des- cribe a technique for identifying and examining SLNs and to report preliminary results. Materials and method: Twenty consecutive patients we re included pro s p e c t ive ly. Ly m p h o s c i n t i grap hy was performed after injecting Nanocis® on D0. A handheld gamma probe was used for sentinel node identification during surgery. Sentinel nodes were examined by standard histology and immunohisto- chemistry. Neck dissection was performed routinely. Results:SLNs were identified in 19 patients. In the 4 patients with micrometastases, in-depth node studies led to pN upstaging from pN0 to pN2 in 1 patient and from pN1 to pN2 in 3 patients. No false negatives (negative SLN and positive dissection) were recorded. Conclusion:The technique described in this study may improve node staging. A multicenter study is needed to confirm these preliminary findings and to evaluate outcomes according to node stage.