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(1) Background: triple-negative breast cancer (TNBC) remains a clinical and therapeutic challenge primarily affecting young women with poor prognosis. TNBC is currently treated as a single entity but presents a very diverse profile in terms of prognosis and response to treatment. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose ([18F]FDG) is gaining importance for the staging of breast cancers. TNBCs often show high [18F]FDG uptake and some studies have suggested a prognostic value for metabolic and volumetric parameters, but no study to our knowledge has examined textural features in TNBC. The objective of this study was to evaluate the association between metabolic, volumetric and textural parameters measured at the initial [18F]FDG PET/CT and disease-free survival (DFS) and overall survival (OS) in patients with nonmetastatic TBNC. (2) Methods: all consecutive nonmetastatic TNBC patients who underwent a [18F]FDG PET/CT examination upon diagnosis between 2012 and 2018 were retrospectively included. The metabolic and volumetric parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG) and the textural features (entropy, homogeneity, SRE, LRE, LGZE, and HGZE) of the primary tumor were collected. (3) Results: 111 patients were enrolled (median follow-up: 53.6 months). In the univariate analysis, high TLG, MTV and entropy values of the primary tumor were associated with lower DFS (p = 0.008, p = 0.006 and p = 0.025, respectively) and lower OS (p = 0.002, p = 0.001 and p = 0.046, respectively). The discriminating thresholds for two-year DFS were calculated as 7.5 for MTV, 55.8 for TLG and 2.6 for entropy. The discriminating thresholds for two-year OS were calculated as 9.3 for MTV, 57.4 for TLG and 2.67 for entropy. In the multivariate analysis, lymph node involvement in PET/CT was associated with lower DFS (p = 0.036), and the high MTV of the primary tumor was correlated with lower OS (p = 0.014). (4) Conclusions: textural features associated with metabolic and volumetric parameters of baseline [18F]FDG PET/CT have a prognostic value for identifying high-relapse-risk groups in early TNBC patients.

(1) Background: triple-negative breast cancer (TNBC) remains a clinical and therapeutic challenge primarily affecting young women with poor prognosis. TNBC is currently treated as a single entity but presents a very diverse profile in terms of prognosis and response to treatment. Positron emission tomography/computed tomography (PET/CT) with

International audience; BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease characterized by elastic fiber fragmentation and ectopic calcification. There is growing evidence that vascular calcification is associated with inflammatory status and is enhanced by inflammatory cytokines. Since PXE has never been considered as an inflammatory condition, no incidence of chronic inflammation leading to calcification in PXE has been reported and should be investigated. In atherosclerosis and aortic stenosis, positron emission tomography combined with computed tomographic (PET-CT) imaging has demonstrated a correlation between inflammation and calcification. The purpose of this study was to assess skin/artery inflammation and calcification in PXE patients. Methods: 18F-FluroDeoxyGlucose (18F-FDG) and 18F-Sodium Fluoride (18F-NaF) PET-CT, CT-imaging and Pulse wave velocity (PWV) were used to determine skin/vascular inflammation, tissue calcification, arterial calcium score (CS) and stiffness, respectively. In addition, inorganic pyrophosphate, high-sensitive C-reactive protein and cytokines plasma levels were monitored.RESULTS: In 23 PXE patients, assessment of inflammation revealed significant 18F-FDG uptake in diseased skin areas contrary to normal regions, and exclusively in the proximal aorta contrary to the popliteal arteries. There was no correlation between 18F-FDG uptake and PWV in the aortic wall. Assessment of calcification demonstrated significant 18F-NaF uptake in diseased skin regions and in the proximal aorta and femoral arteries. 18F-NaF wall uptake correlated with CS in the femoral arteries, and aortic wall PWV. Multivariate analysis indicated that aortic wall 18F-NaF uptake is associated with diastolic blood pressure. There was no significant correlation between 18F-FDG and 18F-NaF uptake in any of the artery walls.CONCLUSION: In the present cross-sectional study, inflammation and calcification were not correlated. PXE would appear to more closely resemble a chronic disease model of ectopic calcification than an inflammatory condition. To assess early ectopic calcification in PXE patients, 18F-NaF-PET-CT may be more relevant than CT imaging. It potentially constitutes a biomarker for disease-modifying anti-calcifying drug assessment in PXE.

Purpose For differentiating tumor from inflammation and normal tissues, fluorodeoxyglucose ([18F]FDG) dual time point PET could be helpful. Albeit [18F]FLT is more specific for tumors than [18F]FDG; we explored the role of dual time point [18F]FLT-PET for discriminating benign from malignant tissues. Methods Before any treatment, 85 womens with de novo unifocal breast cancer underwent three PET acquisitions at 33.94 ± 8.01 min (PET30), 61.45 ± 8.30 min (PET60), and 81.06 ± 12.12 min (PET80) after [18F]FLT injection. Semiquantitative analyses of [18F]FLT uptake (SUV) were carried out on tumors, liver, bone marrow (4th thoracic vertebra (T4) and humeral head), descending thoracic aorta, muscle (deltoid), and contralateral normal breast. Repeated measures ANOVA tests and Tukey’s posttests were used to compare SUVmax of each site at the three time points. Results There was a significant increase in SUVmax over time for breast lesions (5.58 ± 3.80; 5.97 ± 4.56; 6.19 ± 4.42; p < 0.0001) (m ± SD for PET30, PET60, and PET80, respectively), and bone marrow (for T4, 8.21 ± 3.17, 9.64 ± 3.66, 10.85 ± 3.63, p < 0.0001; for humeral head, 3.36 ± 1.79, 3.87 ± 1.89, 4.39 ± 2.00, p < 0.0001). A significant decrease in SUVmax over time was observed for liver (6.79 ± 2.03; 6.24 ± 1.99; 5.57 ± 1.74; p < 0.0001), muscle (0.95 ± 0.28; 0.93 ± 0.29; 0.86 ± 0.20; p < 0.027), and aorta (1.18 ± 0.34; 1.01 ± 0.32; 0.97 ± 0.30; p < 0.0001). No significant difference was observed for SUVmax in contralateral breast (0.8364 ± 0.40; 0.78 ± 0.38; 0.80 ± 0.35). Conclusion [18F]FLT-SUVmax increased between 30 and 80 min only in proliferating tissues. This could be helpful for discriminating between residual tumor and scar tissue.

Purpose For differentiating tumor from inflammation and normal tissues, fluorodeoxyglucose ([18F]FDG) dual time point PET could be helpful. Albeit [18F]FLT is more specific for tumors than [18F]FDG; we explored the role of dual time point [18F]FLT-PET for discriminating benign from malignant tissues. Methods Before any treatment, 85 womens with de novo unifocal breast cancer underwent three PET acquisitions at 33.94 ± 8.01 min (PET30), 61.45 ± 8.30 min (PET60), and 81.06 ± 12.12 min (PET80) after [18F]FLT injection. Semiquantitative analyses of [18F]FLT uptake (SUV) were carried out on tumors, liver, bone marrow (4th thoracic vertebra (T4) and humeral head), descending thoracic aorta, muscle (deltoid), and contralateral normal breast. Repeated measures ANOVA tests and Tukey’s posttests were used to compare SUVmax of each site at the three time points. Results There was a significant increase in SUVmax over time for breast lesions (5.58 ± 3.80; 5.97 ± 4.56; 6.19 ± 4.42; p < 0.0001) (m ± SD for PET30, PET60, and PET80, respectively), and bone marrow (for T4, 8.21 ± 3.17, 9.64 ± 3.66, 10.85 ± 3.63, p < 0.0001; for humeral head, 3.36 ± 1.79, 3.87 ± 1.89, 4.39 ± 2.00, p < 0.0001). A significant decrease in SUVmax over time was observed for liver (6.79 ± 2.03; 6.24 ± 1.99; 5.57 ± 1.74; p < 0.0001), muscle (0.95 ± 0.28; 0.93 ± 0.29; 0.86 ± 0.20; p < 0.027), and aorta (1.18 ± 0.34; 1.01 ± 0.32; 0.97 ± 0.30; p < 0.0001). No significant difference was observed for SUVmax in contralateral breast (0.8364 ± 0.40; 0.78 ± 0.38; 0.80 ± 0.35). Conclusion [18F]FLT-SUVmax increased between 30 and 80 min only in proliferating tissues. This could be helpful for discriminating between residual tumor and scar tissue.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder characterized by fragmentation and progressive calcification of elastic fibers in connective tissues, such as the skin, vascular system, and Bruch’s membrane.1 PXE is caused by mutations in the ABCC6 gene, on the short arm of chromosome 16, encoding a transmembrane ATP-binding anion transporter primarily expressed in the liver/kidney.1 Its pathophysiology is unknown, but in several studies, normal tissues exposed to patient with PXE serum/plasma tend to calcify.1 PXE manifestations include yellowish papules on the neck and in large skin folds and cardiovascular complications, such as peripheral artery disease resulting from tunica media calcifications in medium/small-sized arteries.1 Vascular histological studies are limited by poor availability of artery tissue in patients with advanced disease and are unsuitable for longitudinal study of disease progression. Alternative techniques are, therefore, required to investigate the pathogenesis and progression of this condition. In a previous case series, skin and vascular calcification was investigated using 18F-sodium fluoride (18F-NaF) positron emission tomography combined with computed tomographic imaging in 4 patients with PXE.2 18F-flurodeoxyglucose (18F-FDG) has been used in several studies to investigate vascular conditions wherein inflammation is considered essential in the pathogenesis of conditions, such as atherosclerotic plaque.3 Our report hypothesized that in patients with PXE, low-grade chronic inflammation may precede or evolve concomitantly with skin and vascular wall calcification. We report the case of a 42-year-old smoker, …

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José Hureaux,1,2 Franck Lacœuille,3,4 Frédéric Lagarce,1,5 Marie-Christine Rousselet,6 Aurélien Contini,3,4 Patrick Saulnier,1,7 Jean-Pierre Benoit,1,5 Thierry Urban1,2 1Unité Micro et Nanomédecines Biomimétiques (MINT), Université d’Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, 2Université d’Angers, CHU, Pôle Hippocrate, Service de Pneumologie, 3Université d’Angers, CHU, Pôle Signal Image Stérilisation, Service de Médecine nucléaire, 4CRCINA, Université Nantes Université Angers, 5Université d’Angers, CHU, Pôle Hippocrate, Pharmacie, 6Université d’Angers, CHU, Pôlede Biologie-Pathologie, Département de Cytologie et d’Histologie Pathologique, 7Université d’Angers, CHU, Service la Recherche Clinique et Innovation, Angers, France Abstract: Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy. Keywords: lipid nanocapsules, pulmonary drug delivery, biodistribution, toxicity, paclitaxel

Objective To assess the potential use of indium-111 diethylenetriamine pentaacetic acid ( 111 In-DTPA) scintigraphy coupled with computed tomography (CT) for the investigation of intrathecal baclofen (ITB) device malfunction. Design Retrospective study of a case series of patients. Setting Neurosurgical and physical and rehabilitation medicine departments. Participants Patients (N=7) with reduced ITB effectiveness in whom prior conventional radiographs were inconclusive. Intervention Nine 111 In-DTPA scintigraphic studies and 8 CT scans. Planar acquisitions were followed by tomoscintigraphy combined with CT. Main Outcome Measure Progression of the radiotracer in the pump, catheters, and in the subarachnoid space. Results In 7 cases, scintigraphy coupled with CT showed leakage behind the pump, lack of activity outside the pump reservoir, abrupt interruption of activity in the catheter, or abnormal distribution of the radiotracer, thus demonstrating that the drug did not reach its target. Surgical revision confirmed these findings in 5 cases. In 1 case, combined imagery ruled out device dysfunction. In the remaining case, only planar acquisitions were performed, showing correct diffusion of the radiotracer. Conclusions The combination of scintigraphy and CT provides simultaneous functional and anatomic imagery of the device. The slow infusion of the radioisotope mimics the diffusion of baclofen, and this could be a useful method to explore intrathecal device malfunction. Further studies are required to compare scintigraphy coupled with CT, to radiopaque injection followed by fluoroscopy or CT.

Background This study is an assessment of the impact of acquisition times on SUV with [18F]FDG-PET/CT on healthy livers (reference organ with stable uptake over time) and on tumors. Methods One hundred six [18F]FDG-PET/CT were acquired in list mode over a single-bed position (livers (n = 48) or on tumors (n = 58)). Six independent datasets of different durations were reconstructed (from 1.5 to 10 min). SUVmax (hottest voxel), SUVpeak (maximum average SUV within a 1-cm3 spherical volume), and SUVaverage were measured within a 3-cm-diameter volume of interest (VOI) in the right lobe of the liver. For [18F]FDG avid tumors (SUVmax ≥ 5), the SUVmax, SUVpeak, and SUV41% (isocontour threshold method) were computed. Results For tumors, SUVpeak values did not vary with acquisition time. SUVmax displayed significant differences between 1.5- and 5–10-min reconstruction times. SUV41% was the most time-dependent parameter. For the liver, the SUVaverage was the sole parameter that did not vary over time. Conclusions For [18F]FDG avid tumors, with short acquisition times, i.e., with new generations of PET systems, the SUVpeak may be more robust than the SUVmax. The SUVaverage over a 3-cm-diameter VOI in the right lobe of the liver appears to be a good method for a robust and reproducible assessment of the hepatic metabolism.

Purpose This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain a unique theranostic vector for the treatment of Hepatocellular Carcinoma. Methods Optimal labeling conditions and composition of freeze-dried kits were defined by monitoring the radiochemical purity while varying several parameters. In vitro stability studies were carried out, as well as an in vivo biodistribution as a preliminary approach with the intraarterial injection of 68Ga radiolabeled SBMP into the hepatic artery of DENA-induced rats followed by PET/CT imaging. Results Kits were optimized for 188Re and 68Ga with high and stable radiochemical purity (>95% and >98% respectively). The in vivo preliminary study was successful with more than 95% of activity found in the liver and mostly in the tumorous part. Conclusion SBMP are a promising theranostic agent for the Selective Internal Radiation Therapy of Hepatocellular carcinoma. © 2016 Verger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

International audience; INTRODUCTION: The aim of this work was to map E-selectin expression in a traumatic brain injury model using a newly-designed MR contrast agent. Iron cores, responsible for susceptibility effects and therefore used as T2* contrast agents, need to be coated in order to be stabilized and need to be targeted to be useful. METHODS: We have designed a molecule coating composed, at one end, of bisphosphonate to ensure anchorage of the coating on the iron core and, at the other end, of Fukuda's defined heptapeptide known to target selectin binding sites. CONCLUSION: The synthesized nanoparticles were able to non-invasively target the traumatic brain lesion, inducing a specific T2* decrease of about 25% up to at least 70 min post-injection of the targeted contrast agent.

International audience; 68Ga-labelled peptides imaging has emerged during the last decade. This was possible thanks to innovative development in 68Ge/68Ga generator or bifunctional chelates (BFC) able to complex 68Ga and to be linked to various peptides and thus optimize radiolabelling procedures. This present review focuses on radiolabelling of somatostatine (SMS) analogs with 68Ga for clinical applications. In that sense, is discussed the key parameters influencing the radiolabelling, from the elution of 68Ge/68Ga generator to purification of final product, and through the quality control of 68Ga-SMS analog radiopharmaceuticals, as well as the full automation of the radiolabelling process.

International audience; ObjectifsDéterminer la faisabilité, l’intérêt et la toxicité hématologique de l’administration intratumorale par convection enhanced delivery (CED) de nanocapsules chargées en 188Re (NCL-188Re).Matériels et méthodesL’étude de biodistribution des NCL-188Re vs perrhénate (188ReO4−) a été réalisée sur des souris nude (n=30). Les animaux ont été séparés en 2groupes: injection intratumorale de 188ReO4− pour le premier groupe (n=15, 3MBq) et de NCL-188Re pour le second groupe (n=15, 3MBq). Les animaux ont été sacrifiés à 1h (n=10), 24h (n=10) et 72h (n=10) après l’injection, les organes prélevés et comptés. La toxicité hématologique des NCL-188Re a été évaluée par prises de sang de 50μL (sinus rétro-orbitaire) réalisées à j2, j7, j14et j21après traitement par NaCl (n=4), NCL-188Re (3MBq, n=4), NCL-188Re (6MBq, n=4) et NCL-188Re (12MBq, n=4).RésultatsLa vectorisation par NCL a permis de limiter l’élimination urinaire du 188Re puisque dès 24h post-IV 0,1±0,1% de la dose injectée (%D.I.) vs 81,9±7,5% D.I. sont retrouvés dans les urines pour les formes NCL188Re-SSS et 188ReO4-, respectivement, (p=0,016). Celle-ci permet également de retrouver une activité significativement supérieure dans la tumeur à tous les temps de l’étude. L’administration unique de NCL-188Re a induit une toxicité modérée pour les activités injectées les plus élevées (12MBq) se manifestant principalement par une thrombopénie transitoire de nadir j14–j18. Il n’a pas été observé de toxicité au niveau des autres lignées cellulaires pour les activités administrées de 3et 6MBq.ConclusionsLes résultats obtenus montrent la faisabilité de l’injection intratumorale par CED et l’intérêt de la vectorisation du 188Re par les NCL. Les premiers signes de toxicité hématologiques sont en faveur du fractionnement des doses administrées et d’un meilleur ciblage par fonctionnalisation des NCL aux oestrogènes pour permettre une meilleure rétention tumorale.

International audience; ObjectifsÉvaluation de l’efficacité de l’administration intratumorale par convection enhanced delivery (CED) de nanocapsules chargées en 188Re (NCL-188Re) sur un modèle hétérotopique d’adénocarcinome de l’endomètre (Ishikawa) selon un schéma d’escalade de dose.Matériels et méthodesLes souris (n=40) ont été traitées lorsque le grand axe tumoral a atteint 8mm. Les animaux ont été séparés en 2groupes témoins: injection intratumorale par CED de NaCl (groupe 1; n=8) et de NCL blanches (groupe 2; n=8), et 3groupes traités par injection intratumorale en CED de NCL-188Re (groupe 3; 3MBq; n=8/groupe 4; 6MBq; n=8et groupe 5; 12MBq; n=8). La réponse thérapeutique a été évaluée en mesurant cliniquement et par μIRM (BioSpec 70/20USR 7Tesla Bruker) l’évolution du volume tumoral (VT). Le point limite choisi a été le doublement du VT ou un VT>2150μL.RésultatsLa radiothérapie vectorisée par NCL-188Re a significativement augmenté la médiane de survie des animaux traités des groupes 3, 4et 5, de 290%, 290% et 570%, respectivement, par rapport au groupe 1 (p=0,021; p=0,031; pConclusionsL’injection intratumorale unique par CED de NCL-188Re sur modèle hétérotopique murin de cancer de l’endomètre hormono-dépendant a permis d’obtenir un régression tumorale spectaculaire pour les animaux traités avec une activité de 12MBq. Ces bons résultats seront à confirmer lors d’études dosimétriques et de fractionnement de dose.

International audience; Aim: To evaluate changes in tumour glycolysis measured by positron emission tomography (PET) with [18F]fluoro-desoxyglucose ([18F]-FDG) and in steroid hormone receptor expression measured by PET with 16α-[18F]fluoro-17β-oestradiol ([18F]-FES) following internal radiotherapy with nanoparticles loaded with rhenium-188 (LNC-188Re-SSS) in a preclinical murine model of human endometrial cancer. Materials and methods: Ishikawa endometrial carcinoma cell lines were implanted subcutaneously in nude mice (n=10). D28 after inoculation, mice (n=5) were treated with an intra-tumor injection of LNC-188Re-SSS. Treatment efficiency in the LNC-188Re-SSS group was compared to control group (n=5) in term of tumour growth assessed by clinical palpation and micro-PET/CT imaging. For each mouse, two [18F]-FDG and two [18F]-FES micro-PET/CT were performed on separate imaging days, at baseline before therapy, and two weeks later.Results: Fourteen days after treatment with LNC-188Re-SSS, tumour progression was significantly inhibited compared to the control group (pConclusion: Because after treatment, significant changes in tumour uptake was observed only with [18F]FDG and not with [18F]-FES, [18F]-FES does not appear to be able to monitor the therapeutic effect of internal radiation with LNC-188Re-SSS.

Opinion/Feedback Intrathecal baclofen is now an admitted treatment of generalized and disabling spasticity. Technical incidents of the device remain frequent, mainly due to catheter problems. Consequences can be abrupt with life-threatening withdrawal syndrome or progressive with spasticity reappearance. In case of progressive withdrawal syndrome, the assessment process has to be meticulous to find the cause of inefficiency and to avoid useless revision surgery. This assessment includes medical examination, radiographs, intrathecal baclofen bolus, after what, if no conclusion can be drawn, a more invasive imaging exam has to be performed. Radio-opaque dye study by injecting contrast through the lateral access port is the assessment the most used, but it has some drawbacks as the difficulty to access to the lateral access port. In our experience nuclear medicine assessment with Indium scintigraphy coupled with computed tomography is underused and should be an alternative to other imaging exam. Using our experience, we want to discuss a proposition of diagnostic algorithm for intrathecal baclofen pump inefficiency adding nuclear imaging exam adapted from already existing algorithms.

International audience; Background: Intrathecal baclofen infusion is an established method for the treatment of generalized and disabling spasticity. The most frequent technical problems are due to catheter/pump disconnections, but diagnosis of dysfunction may be difficult.CASE REPORT:We report here the case of a 53-year-old woman with spastic paraplegia treated with intrathecal baclofen. Spasticity remained uncontrolled despite a gradual increase in baclofen dosage. On plain radiographs the distal end of the catheter was found to be pointing downwards with the catheter tip at level L5 and no apparent disconnection or failure. Indium111 diethylenetriamine penta-acetic acid (DTPA) scintigraphy combined with computed tomography revealed that the activity of the radioisotope was highest next to the first sacral vertebra and that there was no leakage. Radioisotope activity above the lumbar level was very low. The catheter tip was therefore repositioned to level T7. One month later, spasticity was well controlled and a second scintigraphy confirmed high activity of intrathecal radioisotope up to the basal cisterns.Discussion: The combination of Indium111 DTPA scinti-graphy with computed tomography allows anatomical and functional investigation of intrathecal drug administration. In this case report this approach showed that the inefficiency of intrathecal baclofen was due to the caudal orientation of the catheter.

Purpose The aim of this prospective study was to evaluate whether [18F]FDG-PET/CT, performed within two weeks of starting erlotinib therapy can predict tumor response defined by RECIST 1.1 criteria after 8 weeks of treatment in patients with inoperable (stage IIIA to IV) non-small cell lung cancer patients. Patients and Methods Three [18F]FDG-PET/CT scans were acquired in 12 patients before (5±4 days) and after 9±3 days (early PET) and 60±6 days (late PET) of erlotinib therapy. Conventional evaluation, including at least chest CT (baseline versus after 8 weeks of treatment), was performed according to RECIST 1.1 criteria. Change in [18F]FDG uptake was compared with conventional response, progression-free survival (PFS), and overall survival (OS). Results By using ROC analysis, the Area Under the Curve for prediction of metabolic non-progressive disease (mNP) by early PET was 0.86 (95% CI, 0.62 to 1.1; P = 0.04) at a cut-off of 21.6% reduction in maximum Standardized Uptake Value (SUVmax). This correctly classified 11/12 patients (7 with true progressive disease; 4 with true non-progressive disease; 1 with false progressive disease). Non-progressive disease after 8 weeks of treatment according to RECIST 1.1 criteria was significantly more frequent in patients classified mNP (P = 0.01, Fisher's exact test). mNP patients showed prolonged PFS (HR = 0.27; 95% CI, 0.04 to 0.59; P

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International audience; The visualization of symmetric structure by [18F]-FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET), corresponding to adipose density in computed tomography (CT), has led to the idea that Brown Adipose Tissue (BAT) could be present in adult human.This article studies the FDG uptake in a mice model deficient on Uncoupling Protein 1 (UCP1), in a simple thermal activation protocol.Methods:FDG were injected in mice, control and knock out (K.O.) for the UCP1. Before imaging mice were placed either in cold or warm environment. BAT uptake was evaluated by ratio named RISC.Results:In warm condition, mean value of the Ratio of Inter-Scapular uptake (RISC) was 1.34 +/﹣0.27. After cold exposure, RISC increased 2 fold for control mice, male K.O. did not increase their RISC, female K.O. increased their RISC up to 2.45.Conclusion:Our study brought a further confirmation that FDG-PET visualised activated Brown Adipose Tissue. It gives a direct proof of the role of UCP1 in this process. The FDG uptake by cold female K.O.mice was unexpected.

International audience; UNLABELLED: A multi-centre trial using PET requires the analysis of images acquired on different systems We designed a multi-centre trial to estimate the value of 18F-FLT-PET to predict response to neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. A calibration check of each PET-CT and of its peripheral devices was performed to evaluate the reliability of the results.MATERIAL AND METHODS: 11 centres were investigated. Dose calibrators were assessed by repeated measurements of a 68Ge certified source. The differences between the clocks associated with the dose calibrators and inherent to the PET systems were registered. The calibration of PET-CT was assessed with an homogeneous cylindrical phantom by comparing the activities per unit of volume calculated from the dose calibrator measurements with that measured on 15 Regions of Interest (ROIs) drawn on 15 consecutive slices of reconstructed filtered back-projection (FBP) images. Both repeatability of activity concentration based upon the 15 ROIs (ANOVA-test) and its accuracy were evaluated.RESULTS: There was no significant difference for dose calibrator measurements (median of difference -0.04%; min = -4.65%; max = +5.63%). Mismatches between the clocks were less than 2 min in all sites and thus did not require any correction, regarding the half life of 18F. For all the PET systems, ANOVA revealed no significant difference between the activity concentrations estimated from the 15 ROIs (median of difference -0.69%; min = -9.97%; max = +9.60%).CONCLUSION: No major difference between the 11 centres with respect to calibration and cross-calibration was observed. The reliability of our 18F-FLT multi-centre clinical trial was therefore confirmed from the physical point of view. This type of procedure may be useful for any clinical trial involving different PET systems.

Objectifs En cas de recrudescence de la spasticite chez un patient porteur d’une pompe a baclofene, une resistance au traitement, une pathologie intercurrente et un dysfonctionnement (mecanique ou non) du dispositif d’administration intrathecale doivent etre evoques. Le but de ce travail a ete d’evaluer l’interet d’une scintigraphie a l’Indium 111-DTPA avec TEMP/TDM pour l’etude du fonctionnement de ce systeme. Materiels et methodes Sept examens scintigraphiques ont ete realises chez 6 patients (4 hommes et 2 femmes, âge : min : 27 ans, max : 73 ans). Une dose mediane de 30 MBq (min : 18 MBq, max : 35 MBq) d’Indium 111-DTPA a ete injectee dans le reservoir des pompes sans interrompre l’administration du baclofene. Des cliches statiques et TEMP/TDM ont ete realises a differents temps jusqu’a 7 jours apres injection. Resultats Trois cas de dysfonctionnement de catheter ( n = 2) ou de pompe ( n = 1), 2 cas de distribution anormale dans le liquide cephalorachidien et un aspect normal ont ete observes en scintigraphie et confirmes par le suivi clinique et les donnees operatoires. L’acquisition TEMP/TDM est utile pour localiser la cause du dysfonctionnement. Le temps d’arrivee theorique du radiotraceur dans les espaces sous-arachnoidiens depend du debit de baclofene, son calcul est necessaire afin d’adapter les temps d’acquisition. Conclusions La scintigraphie a l’Indium 111-DTPA pourrait etre un examen utile pour la comprehension et la prise en charge des recrudescences de spasticite chez les patients porteurs d’un dispositif d’infusion intrathecale de baclofene.

Objectifs La radiotherapie interne selective (SIRT) du carcinome hepatocellulaire (CHC) est basee sur l’utilisation de 2 vecteurs. Les differences, en taille et en morphologie, entre ces 2 vecteurs (macro-agregats d’albumine humaine [MAA] marques au 99mTc et microspheres marquees a l’90Y) peuvent conduire a observer des differences importantes de biodistribution, problematiques pour predire d’eventuels effets secondaires et pour une evaluation dosimetrique pre-therapeutique de precision. Le but de ce travail etait de developper, valider et optimiser le radiomarquage de microparticules a base d’amidon (SBMP) par le 188Re et le 68Ga sous la forme de kits de radiomarquage prets a l’emploi, afin d’obtenir un vecteur theranostique unique pour la SIRT du CHC. Materiels et methodes La formulation et la composition de kits lyophilises pour le radiomarquage au 188Re et au 68Ga ont ete optimisees en evaluant la purete radiochimique (PRC) apres radiomarquage. La stabilite in vitro a ete evaluee en milieu serique et en presence d’agents complexants. Comme preuve de concept, une etude de la biodistribution in vivo (TEP/CT) des microparticules radiomarquees au 68Ga (68Ga-SBMP) injectees par voie intra-arterielle dans un modele d’hepatocarcinome chimio-induit chez le rat a ete realisee (n = 3). Resultats Toutes les reactions de radiomarquage au 188Re (n = 46) et au 68Ga (n = 34) ont ete realisees a temperature ambiante. Des kits pret-a-l’emploi dedies au radiomarquage par le 188Re ont ete developpes avec une PRC > 95 % avec la composition suivante : 300 mg de SBMP, 1 mg de SnCl2 et 30 mg de gluconate. Une PRC ≥ 98 % a ete obtenue avec 100 mg de SBMP par marquage direct des kits avec un eluat de 68GaCl3. Ces resultats ont ete optimises en ajoutant un tampon acetate de pH4.1 lors du marquage pour atteindre une PRC > 99 % apres 5 min de reaction. Les acquisitions realisees en TEP, 20 min apres l’injection de 68Ga-SBMP dans l’artere hepatique des rats, ont mis en evidence une bonne stabilite du marquage in vivo avec une activite hepatique localisee au niveau de la tumeur. Conclusions Les microparticules SBMP, en etant capable d’etre radiomarquees rapidement, de maniere reproductible, sous forme de kits prets a l’emploi, par du 188Re et du 68Ga, se revelent etre un outil theranostique prometteur pour le traitement du carcinome hepatocellulaire.

International audience; The aim of this work was to develop a new microparticulate system able to form a complex with radionuclides with a high yield of purity for diagnostic or therapeutic applications. Owing to its properties potato starch was chosen as starting material and modified by oxidization and coupling of a ligand (polyamine) enabling modified starch to chelate radionuclides. The choice of suitable experiments was based on a combination of a Rechtschaffner experimental design and a surface response design to determine the influence of experimental parameters and to optimize the final product. Starch-based microparticle formulations from the experimental plans were compared and characterized through particle size analysis, scanning electron microscopy, elemental analysis and, for the most promising formulations, by in vitro labeling stability studies and determination of free polyamine content or in vivo imaging studies. The mechanism of starch-based microparticle degradation was identified by means of size measurements. The results of the Rechtschaffner design showed the positive qualitative effect of the temperature and the duration of coupling reaction whereas surface response analysis clearly showed that, by increasing the oxidization level and starch concentration, the nitrogen content in the final product is increased. In vitro and in vivo characterization led to identification of the best formulation. With a size around 30 mum, high radiochemical purity (over 95%) and a high signal-to-noise ratio (over 600), the new starch-based microparticulate system could be prepared as ready-to-use kits and sterilized without modification of its characteristics, and thus meet the requirement for in vivo diagnostic and therapeutic applications.

International audience; BACKGROUND: In 2008, American consensus recommendations for performing gastric emptying (GE) scintigraphy were published. It was recommended that data are acquired only at 0, 1, 2, and 4 h and that the results are expressed as percentages of meal retention. Until now, it was established that the GE time-activity curves should have many points (every 10, 15, or 20 min) to reflect the GE process accurately and to be optimally adjusted by a mathematical model. In this study, we have evaluated the curve fitting using only a few points as proposed by the consensus protocol. MATERIALS AND METHODS: GE scintigraphy tests of 224 patients were retrospectively analyzed. Two curve fittings were done for each patient, either using data acquired every 20 min or using data acquired every hour. A comparison of these two methods was made based on the values of the computed GE parameters. RESULTS: We observed strong correlations between the two methods (r=0.81-0.99, P

International audience

Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin. However, other radiolabeled analogs have also been developed and assessed in vitro and in vivo and some of them are already in clinical use. For instance, radiolabeled analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substance P (SP), cholecystokinin (CCK), integrins… This review focuses on gallium-68radiolabeled peptides developed for PET imaging, except for somatostatin analogs, which are discussed in another article., Le ciblage de récepteurs avec des peptides radiomarqués est devenu très important en oncologie nucléaire au cours de ces dernières années. Les peptides les plus fréquemment utilisés en clinique sont les analogues de la somatostatine. Cependant, d’autres analogues radiomarqués ont également été développés et évalués in vitro et in vivo et pour certains déjà en clinique. Il s’agit par exemple de l’alpha-melanocyte-stimulating hormone (alpha-MSH), de la neurotensine, du peptide intestinal vasoactif (VIP), de la bombésine, de la substance P (SP) et de la cholécystokinine (CCK), des intégrines… Cette revue se focalise sur les peptides radiomarqués au gallium-68, développés pour l’imagerie TEP, en dehors des analogues de la somatostatine, qui sont discutés dans un autre article.

International audience; PURPOSE:In order to avoid the microbiological risks linked to human serum albumin macroaggregates (MAA) used for lung perfusion scintigraphy, we developed a new starch-based Tc-99m potential radiopharmaceutical.METHODS:Microparticles were prepared from oxidised starch coupled to natural polyamine for Tc-99m complexation. Suspensions were formulated as ready-to-use kits for easy one-step labelling procedures.RESULTS:Particle-size analysis, electron microscopy, and confocal microscopy were performed for microparticle characterisation, and gave a typical size distribution ranging from 7 to 63 microm, with a homogenous population of spherical or oval-shaped microparticles. Radiochemical purity exceeded 95%, and was stable for at least 8 h. When challenged with histidine and human plasma, labelling was also stable. Dynamic scintigraphic acquisitions and biodistribution studies conducted on healthy Wistar rats showed a tracer accumulation with more than 80% of the ID in the lungs after 15 min.CONCLUSIONS:With clinically significant characteristics such as a lung half-life of 3 h, a lung-to-vascular ratio of 900, and a lung-to-liver ratio of 90, starch-based microparticles exhibit all the qualities for an effective new lung perfusion agent.

International audience

As non-phagocytic eukaryotic cells can internalize particles μm in size, small size (25 to 110 nm) lipid nanocapsules (LNC) are proposed for the intracellular drug delivery of anticancer drugs to cancer cells. LNC ofdifferent diameters were loaded with etoposide or paclitaxel and subsequently tested for drug release kinetics and their efficiency to reduce cancer cell growth in cell culture. Relative high drug loads could be achieved and sustained drug release can be provided over a period ofseveral days (etoposide) up to a few weeks (paclitaxel). While particle size exhibited only minor influences on the release kinetics, higher initial drug load led to a distinctly lower burst release. In a cancer cell culture model, etoposide or paclitaxel LNC showed a 4-fold or 40-fold higher efficiency, respectively than the drug solution while blank LNC were found to be less toxic than the pure drug at equivalent concentrations. The uptake and intracellular accumulation ofLNC was confirmed by confocal laser scanning microscopy after fluorescence labeling of the nanocarriers. This nanoparticulate system is able to achieve efficient intracellular drug concentrations and seems to be therefore a promising therapeutic approach in cancer treatment.

International audience; Paclitaxel-loaded lipid nanocapsules (PX-LNC) exhibit interesting in vitro characteristics with improved antitumoral activity compared with free PX formulation. Biodistribution studies were realized with the use of (14)C-trimyristin ((14)C-TM) or (14)C-phosphatidylcholine ((14)C-PC) whereas antitumoral activity of PX-LNC formulations was based on the animal survival in a chemically induced hepatocellular carcinoma (HCC) model in Wistar rats. Blood concentration-time profiles for both labeled (14)C-TM-LNC and (14)C-PC-LNC were similar; the t(1/2) and MRT values (over 2h and close to 3h, respectively, for both formulations) indicated the long circulating properties of the LNC carrier with a slow distribution and elimination phase. Survival curves of paclitaxel treated groups showed a statistical significant difference compared to the control survival curve (P=0.0036 and 0.0408). Animals treated with 4x 70 mg/m(2) of PX-LNC showed the most significant increase in mean survival times compared to the controls (IST(mean) 72%) and cases of long-term survivors were preferentially observed in the PX-LNC treated group (37.5%; 3/8). These results demonstrate the great interest to use LNC as drug delivery system for paclitaxel, permitting with an equivalent therapeutic efficiency to avoid the use of excipients such as polyoxyethylated castor oil for its formulation.

International audience; Introduction.– Intrathecal baclofen (ITB) infusion is an established method for the treatment of diffuse and disabling spasticity. The most frequent technical problems are due to catheter/pump dysconnections and diagnosis of dysfunction may be difficult.Observation.– We report the case of a 53-years-old woman suffering from multiple sclerosis with spastic paraplegia treated with ITB pump. Spasticity remained uncontrolled despite a gradual increase of ITB dosage up to 850μg/day. Tests with baclofen infusion by lumbar puncture (150μg) refuted any resistance to this drug. Plain films found a distal catheter directed downward with a catheter tip at L5 level without apparent disconnection or failure. An Indium 111 DTPA scintigraphy coupled with a tomodensitometry was performed. It was found that the activity of the radioisotope was maximal next to the first sacral vertebra related with the atypical orientation of the intrathecal catheter distal extremity. No leakage of the product was revealed. Very low activity of the radioisotope was observed above the lumbar level. The catheter was then replaced at T7 level. One month later, spasticity was well controlled. Six months later, a second Indium111 DTPA scintigraphy confirmed a high activity of intrathecal radioisotope up to the basal cisterns.Discussion.– This observation emphasizes the importance of Indium111 DTPA scintigraphy coupled with a tomodensitometry in the etiologic diagnosis of uncontrolled spasticity in patients with ITB pump. Baclofen stagnation in the dural sac shown in these investigations is related with the orientation of the catheter.

International audience; Aim: To evaluate the biodistribution, the toxicity, the dosimetry and the antitumor efficacy of intra-tumoral injection of rhenium-188 loaded nanoparticles (LNC-188Re-SSS) by CED. Materials and methods: Ishikawa endometrial carcinoma cell lines were implanted subcutaneously in nude mice (n=70). For biodistribution and efficacy studies CED procedure was realized at D28 after tumour implantation. CED was performed using an osmotic pump (0.5μL/min for 20 minutes) after immobilisation of anaesthetized mice on a stereotactic frame. For biodistribution studies, animals (n=30) were injected by CED either with 3MBq of 188ReO4- (n=15) or LNC-188Re-SSS (n=15) and sacrificed at 1h (n=10), 24h (n=10) or 72h (n=10). For efficacy studies, control group mice were injected by CED with saline (n=8) or blank LNC (n=8) and treated group mice were injected with escalating dose of LNC-188Re-SSS: 3MBq (n=8), 6 MBq (n=8) or 12 MBq (n=8). Efficacy on tumour growth was assessed by clinical palpation and μMRI. The time for the tumour volume doubling was chosen as endpoint, leading to the euthanasia of the animal. The physical dose deposited in the tumour for each treated animal was estimated by Monte Carlo simulation (Geant4) using measured biodistribution and μMRI tumour volumes,. Haematological toxicity in mice was evaluated using blood sampling of 50μL (retro-orbital sinus) at D2, D7, D14 and D21 after treatment with saline (n=4) and after treatment with LNC-188Re-SSS, 3MBq (n=4), 6 MBq (n=4) or 12 MBq (n=4). Results: Nanovectorization of 188Re combined with CED allowed the confinement of more than 30 % of ID in the tumour limiting therefore urinary excretion of 188Re since 0,1% versus 81,9% of ID were excreted in urine 24h after CED of LNC-188Re-SSS and 188ReO4- respectively (p=0.016). Nanovectorized radiotherapy has drastically increased the median survival time compared with control group. Animals whose tumor received a dose higher than 69 Gy (69-340 Gy) showed an ISTmedian of + 933%, whereas animals whose tumor received a dose lower than 69 Gy (21-67Gy) showed an ISTmedian of + 391%. Complete response with eradication of the tumor was observed in 4/12 (33.3%) animals of the former group. Depletion of platelets was observed following LNC-188Re-SSS injection with a time to nadir between D14-D21 whereas transient lymphocyte depletion was only observed at D7 for the highest administered activities (12MBq).Conclusion: CED of LNC-188Re-SSS demonstrates interesting biodistribution properties and high efficacy in a model of human endometrial carcinoma.