Etude de l'association radioimmunothérapie chimiothérapie hyperthermique dans les carcinoses péritonéales de petite taille d'origine colique : (étude in vitro)

Le seul traitement améliorant la survie des patients atteints de carcinose colorectale est, au prix d'une forte morbimortalité, la chimiothérapie hyperthermique intrapéritonéale (CHIP) associée à une cytoreduction chirurgicale. L'ajout de la radioimmunothérapie (RIT) en administration concomitante à la CHIP pourrait augmenter l'efficacité de la technique ou permettre de diminuer la morbidité en diminuant les doses de chimiothérapie. Le but de ce travail est d'étudier l'association in vitro. Matériel et méthodes - Pour la RIT, l'anticorps 35A7, spécifique de l'ACE, a été marqué à l'iode 125 (émetteur Auger). Chimiothérapies testées: oxaliplatine, cisplatine, mitomycine C. Des tests de survie clonogénique sur des cellules LS 174" ont été réalisés de carcinome colique humain pour évaluer l'efficacité des traitements. Le temps de traitement est de 1 h à 37 OC ou 42 oC pour simuler la CHIP. L'efficacité de la RIT seule a été testée puis l'association RIT-chimiothérapie. Résultats - La RIT est efficace à 37 et à 42 oC, la diminution de la survie est de 23 à 44 %. L'étude de l'association RIT-chimiothérapie met en évidence un apport significatif de la RIT aussi bien à 37C qu'à 42 C (pour les 3 molécules testées) la diminution de la survie est de 21 à 53 %. Conclusion - Sur la lignée cellulaire LS 174T, on met en évidence une efficacité significative de la RIT seule à 37 oC et à 42 oC ainsi qu'un apport de l'ajout de RIT à la chimiothérapie proche de 30 %, en faveur d'un effet additif. Les résultats de l'étude sont en faveur de l'intérêt de l'ajout de la RIT à la CHIP in vitro, d'où l'importance d'études in vivo de l'association RIT-CHIP.MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Morphodensitométrie osseuse à géométrie cone beam (principe, mise en œuvre et évaluation médico-technique)

Le but de ce travail est d'évaluer les possibilités offertes par la géométrie cone beam, récemment apparue en ostéodensitométrie, pour réaliser, au cours d'un même examen, une analyse de la morphométrie et de l'architecture osseuse en plus de l'analyse densitométrique. Les mesures dosimétriques sont proches de celles des fan beam. Les performances densitométriques sont également du même ordre in vitro et au niveau des hanches, la reproductibilité étant moindre au niveau lombaire. Nous avons proposé une méthode de correction de l'agrandissement des images pour optimiser l'analyse morphométrique. S'il existe une corrélation entre des paramètres de texture et les paramètres morphométriques sur radiographies simulées, nos résultats sont peu reproductibles sur radiographies réelles avec un capteur présentant des pixels de 100 m de côté. Cette technologie est apparue bien adaptée à l'étude du petit animal.The purpose of this paper is to evaluate the possibility of the cone beam geometry in order to evaluate with a single examination the bone morphometry architecture and density. The dosimetry measurements are in the same range as those obtained using fan beam densitometers. The densitometry evaluation is equally in the same range in vitro and for patient hip examination, the lumbar reproducibility being worse. A solution was proposed in order to improve the morphometric evaluation. If a correlation was found between textural and morphological parameters on simulated radiographs, with real radiographs our results are not reproducible with a 100 m pixels size detector. This technology appeared to be adapted for the small animal studies.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Consciousness assessment by activated cerebral 18F-FDG PET complemented with the Wessex head injury matrix (WHIM) in patients with disorder of consciousness (DOC)

International audienceObjectiveCerebral 18F-FDG PET complements bedside examination with behavioural scales in patients with DOC enabling better functional categorization. We realized a resting PET, then another after motor/visual activation, in patients with DOC according to their clinical course.Material/patients and methodsIt is a retrospective mono central study in our acute inpatients rehabilitation unit between 2011 and 2014. Our group consists of 14 patients (whom 5 women) with DOC, 18–70 years old at moment of brain injury (6 severe TBI, 4 anoxia, 3 hemorrhagic and 1 ischemic major strokes). All had months after brain lesions (average delay 186 days), DOC assessment by the Wessex head injury matrix (WHIM), a basal resting state PET, followed by an activated one consisting on providing motor or visual stimulation during second PET. Distant WHIM was performed at least 6 months after (average 14.8 months). We defined 3 groups: (1) WHIM at [1–14], (2) WHIM at [15–29] and (3) WHIM at [30–58]. We analysed, by compared T test of each patient, metabolic increment between basal and activated PET-scan according to clinical course.ResultsAll patients had initial significant increase of metabolism in the activated PET-scan compared with basal ones, but patterns were not always consistent with assigned task. But this significant activation (FWE [P < 0,005]) was particularly located in left occipital, parietal and temporal associative areas, among patients with further best clinical course.Discussion - conclusionAll sever DOC had metabolic increase on activated PET-scan during first year post injury (average 6 months). Among patients with best clinical course we noticed that initial increased metabolism was located in left visual associative cortex and language/phonology treatment areas

FDG-PET in Creutzfeldt-Jakob disease: Analysis of clinical-PET correlation

International audienceOBJECTIVE:To assess the relationship between clinical pattern and cerebral glucose metabolism on [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in Creutzfeldt-Jakob disease (CJD).METHODS:Predefined clinical signs (ataxia, visual, pyramidal, myoclonus, limb apraxia, limb dystonia, sensory, parkinsonism, and corticobasal syndrome [CBS]) and FDG-PET data were assessed in consecutive CJD patients. Two types of statistical parametric mapping (SPM) analyses, using stringent level of significance p < 0.001 and extent threshold of 100 voxels, were performed: one comparing CJD patients presenting specific sign against CJD patients without this specific sign (inter-CJD analysis), and one comparing CJD patients with specific sign against 18 healthy controls (CJD-control analysis).RESULTS:Fifteen CJD patients (11 probable and two histologically proven sporadic and two genetic CJD) were analyzed. CJD-control analysis of the entire CJD group showed lateralized frontal and parietal hypometabolism. When analyzing clinical CJD subgroups, inter-CJD analyses showed hypometabolism in more restricted areas than on CJD-control analyses. For CJD patients presenting with ataxia, visual signs and CBS (and CBS-associated signs), additional hypometabolic areas probably related to the specific signs were identified: pons and middle cerebellar peduncles in patients with ataxia; occipital cortex in patients with visual signs; and prerolandic and lateral parietal cortex in patients with CBS. For pyramidal signs, sensory loss, and parkinsonism, no abnormalities in brain areas typically involved in these signs were observed.CONCLUSION:In addition to lateralized frontal and parietal hypometabolism previously reported in CJD and observed here, hypometabolism in brain areas related to some specific signs (i.e. ataxia, visual signs, and CBS) is also seen

Comparison of the Lunar Prodigy and Stratos DR dual-energy X-ray absorptiometers to assess regional bone mineral density

International audienc

A Recanalized Umbilical Vein Hypermetabolic Thrombosis Mimicked an Hepatocellular Carcinoma Recurrence

International audienceA transarterial left hepatic artery radioembolization involving 90Y microspheres was performed on a cirrhotic man with hypermetabolic 18F-FDG segment III hepatocellular carcinoma. During the 18F-FDG PET/CT follow-up, the disappearance of the hypermetabolic lesion was initially observed. Then, a focal segment III hypermetabolism reappeared mimicking a recurrence before disappearing without any treatment. Finally, the hepatic MRI demonstrated that the transitory segment III hypermetabolism matched a thrombus of the dilated recanalized umbilical vein

Introduction to Radiobiology of Targeted Radionuclide Therapy

International audienceDuring the last decades, new radionuclide-based targeted therapies have emerged as efficient tools for cancer treatment. Targeted radionuclide therapies (TRTs) are based on a multidisciplinary approach that involves the cooperation of specialists in several research fields. Among them, radiobiologists investigate the biological effects of ionizing radiation, specifically the molecular and cellular mechanisms involved in the radiation response. Most of the knowledge about radiation effects concerns external beam radiation therapy (EBRT) and radiobiology has then strongly contributed to the development of this therapeutic approach. Similarly, radiobiology and dosimetry are also assumed to be ways for improving TRT, in particular in the therapy of solid tumors, which are radioresistant. However, extrapolation of EBRT radiobiology to TRT is not straightforward. Indeed, the specific physical characteristics of TRT (heterogeneous and mixed irradiation, protracted exposure, and low absorbed dose rate) differ from those of conventional EBRT (homogeneous irradiation, short exposure, and high absorbed dose rate), and consequently the response of irradiated tissues might be different. Therefore, specific TRT radiobiology needs to be explored. Determining dose-effect correlation is also a prerequisite for rigorous preclinical radiobiology studies because dosimetry provides the necessary referential to all TRT situations. It is required too for developing patient-tailored TRT in the clinic in order to estimate the best dose for tumor control, while protecting the healthy tissues, thereby improving therapeutic efficacy. Finally, it will allow to determine the relative contribution of targeted effects (assumed to be dose-related) and non-targeted effects (assumed to be non-dose-related) of ionizing radiation. However, conversely to EBRT where it is routinely used, dosimetry is still challenging in TRT. Therefore, it constitutes with radiobiology, one of the main challenges of TRT in the future

Diagnostic performances of cervical ultrasound, sestamibi scintigraphy and contrast-enhanced 18 F-fluorocholine positron emission tomography in primary hyperparathyroidism.

International audiencePurpose: Preoperative localization of pathological parathyroids is crucial for a minimally invasive treatment of primary hyperparathyroidism (PHPT). This study compares contrast-enhanced 18F-fluorocholine positron emission tomography (FCH-PET/CT), cervical ultrasound (CU) and conventional scintigraphic imaging modalities (MIBI scintigraphy), combined and individually for preoperative localization of hyper-functional parathyroids in PHPT. The gold standard is histological examination. Methods: Data from consecutive patients with a clinical suspicion of PHPT were retrospectively collected. All three imaging modalities were systematically performed. MIBI scintigraphy, consisted of 99mTc-sestamibi/123I-sodium iodide SPECT/CT, 99mTc-sestamibi/123I-sodium iodide planar subtraction imaging and 99mTc-sestamibi planar dual-phase imaging. The ability of FCH-PET/CT, CU and MIBI scintigraphy to identify a hyper-functional parathyroid and specify the side or identify an ectopic location was noted. Patients underwent surgical exploration if at least one exam was positive. CU + MIBI scintigraphy combined was considered as a positive test if CU and MIBI scintigraphy separately showed a hyper-functional parathyroid gland on the same side, or the same ectopic location, and negative in other cases. The composite judgment criterion for pathological parathyroid combined histological analysis and normalization of PTH and calcium levels. Results: 149 pathological parathyroids were found in 143 of the 144 included patients. FCH-PET/CT diagnosed 148/149 pathological parathyroids. Only four false positives and one false negative were found. The FCH-PET/CT sensitivity of 99.3% was superior to that of CU at 75.2% (P < 0.0001), MIBI scintigraphy at 65.1% (P < 0.0001) and CU + MIBI scintigraphy combined at 89.9%, (P = 0.0009). 5/5 ectopic locations were diagnosed by FCH-PET/CT, 2/5 by MIBI and 0/5 by CU. Accuracy was better for FCH-PET/CT at 98% than CU at 84% (P < 0.0001), MIBI scintigraphy at 81% (P < 0.0001) or CU + MIBI scintigraphy at 91% (P < 0.0001). Among the 72 (50%) patients who had a negative CU + MIBI scintigraphy combined test, FCH-PET/CT correctly identified hyper-functional thyroids in 70 (97.2%) patients. Average FCH-PET/CT hyperfunctional parathyroid uptake was higher than the adjacent thyroid (SULmax 6.45 vs 2.15) (P < 0.0001). Conclusion: Accuracy of FCH-PET/CT is higher than CU and MIBI scintigraphy for localization of hyper-functional parathyroids, justifying the systematic use of FCH-PET/CT as the first-line method for PHPT diagnosis

Corrigendum to "Increased perfusion in supplementary motor area during a REM sleep behaviour episode" [Sleep Med 12(5) (2011) 531-2]

SCOPUS: er.jinfo:eu-repo/semantics/publishe

Therapeutic efficacy of brief intraperitoneal radioimmunotherapy of ovarian cancer using 213Bi-anti MISRII antibodies

Hypothesis: We assessed in in vitro and in vivo models of ovarian cancer the therapeutic efficacy of 16F12 mAbs directed against Mullerian Inhibiting Substance type II receptor (MISRII) radiolabeled with 213Bi Methods: In vitro, both direct and bystander cytotoxic effects were measured using clonogenic assay and standard medium transfer protocol. Typically, Clonogenic survival was assessed in SK-OV-3 donor cells expressing MISRII and exposed for 90 min to 0.06-0.5MBq/mL of 16F12 213Bi-mAbs. Bystander cytotoxicity was measured in recipient cells grown in non-radioactive culture medium preconditioned for 2 hours in the presence of donor cells. DNA double strand breaks (DSBs) were measured in both donor and recipients cells using immunofluorescent detection of gamma-H2AX and of 53BP1. In vivo we explored in athymic nude mice bearing intraperitoneal (IP) MISRII-expressing AN3CA tumor the therapeutic efficacy of brief-intraperitoneal radioimmunotherapy (BIP-RIT, 12.95 - 37 MBq; 37MBq/mg) or of intraperitoneal RIT (IP-RIT; 2.96-12.95 MBq; 37MBq/mg) using 213Bi-16F12. BIP-RIT mimics hyperthermic intraperitoneal chemotherapy as used in clinic. It consists of intraperitoneal injection of high activities of radiolabeled mAbs followed 30 min later by wash of the peritoneal cavity with saline solution to remove unbound radioactivity. The biodistribution of radiolabeled antibodies following IP-RIT (12.95 MBq; 37MBq/mg) or BIP-RIT (37 MBq; 37MBq/mg) was assessed. Results: In vitro we showed in donor cells a strong direct cytotoxicity of 16F12 213Bi-mAbs. A significant bystander cytotoxicity was also measured in recipient cells. Genotoxic effects were also demonstrated as measured by the formation of DNA DSBs in both donor and recipient cells. In vivo, results of biodistribution indicated that tumour uptake of 213Bi-16F12 during BIP RIT was higher than after IP RIT. The tumour-to-blood uptake ratio was 9 versus 3, respectively, one hour post RIT while it decreased down to 3 and 1, respectively, three hours post-RIT. Finally, a similar delay in tumor growth was observed in mice treated with 12.95 MBq of 213Bi-16F12 following IP-RIT or treated with 37 MBq using BIP-RIT. Conclusions: We confirmed in vitro the therapeutic efficacy of newly developed 16F12 213Bi-mAbs. in vivo results indicate that similar therapeutic efficacy and lower toxicity could be obtained with BIP-RIT compared with IP-RIT. BIP-RIT could be a new tool in the therapy of peritoneal carcinomatosis.JRC.G.I.5-Advanced Nuclear Knowledg