UMR 1288 – Imagerie Translationnelle en Oncologie (LITO)

Publications de l’unité

Année de publication : 2018

Sylvain Auvity, Fabien Caillé, Solène Marie, Catriona Wimberley, Martin Bauer, Oliver Langer, Irène Buvat, Sébastien Goutal, Nicolas Tournier (2018 May 12)

P-Glycoprotein (ABCB1) Inhibits the Influx and Increases the Efflux of C-Metoclopramide Across the Blood-Brain Barrier: A PET Study on Nonhuman Primates.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine : 1609-1615 : DOI : 10.2967/jnumed.118.210104 En savoir plus
Résumé

PET imaging using radiolabeled avid substrates of the ATP-binding cassette (ABC) transporter P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of C-metoclopramide, as a model of a weak ABCB1 substrate, in nonhuman primates. The regional brain kinetics of a tracer dose of C-metoclopramide (298 ± 44 MBq) were assessed in baboons using PET without ( = 4) or with ( = 4) intravenous coinfusion of the ABCB1 inhibitor tariquidar (4 mg/kg/h). Metabolite-corrected arterial input functions were generated to estimate the regional volume of distribution (), as well as the influx () and efflux () rate constants, using a 1-tissue-compartment model. Modeling outcome parameters were correlated with image-derived parameters, that is, areas under the regional time-activity curves (AUCs) from 0 to 30 min and from 30 to 60 min (SUV⋅min) and the elimination slope (; min) from 30 to 60 min. Tariquidar significantly increased the brain distribution of C-metoclopramide ( = 4.3 ± 0.5 mL/cm and 8.7 ± 0.5 mL/cm for baseline and ABCB1 inhibition conditions, respectively, < 0.001), with a 1.28-fold increase in ( < 0.05) and a 1.64-fold decrease in ( < 0.001). The effect of tariquidar was homogeneous across different brain regions. The parameters most sensitive to ABCB1 inhibition were (2.02-fold increase) and AUC from 30 to 60 min (2.02-fold increase). correlated significantly ( < 0.0001) with AUC from 30 to 60 min ( = 0.95), with AUC from 0 to 30 min ( = 0.87), and with ( = 0.62). C-metoclopramide PET imaging revealed the relative importance of both the influx hindrance and the efflux enhancement components of ABCB1 in a relevant model of the human BBB. The overall impact of ABCB1 on drug delivery to the brain can be noninvasively estimated from image-derived outcome parameters without the need for an arterial input function.

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Duc-Loc Nguyen, Catriona Wimberley, Charles Truillet, Benoit Jego, Fabien Caillé, Géraldine Pottier, Raphaël Boisgard, Irène Buvat, Viviane Bouilleret (2018 Apr 20)

Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: Toward identification of optimal treatment windows.

Epilepsia : 1234-1244 : DOI : 10.1111/epi.14083 En savoir plus
Résumé

Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process. Neuroinflammation plays an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation biomarkers such as translocator protein 18 kDa (TSPO) can be potent epilepsy biomarkers. TSPO is associated with reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral HS and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that longitudinal imaging using TSPO positron emission tomography (PET) with F-DPA-714 could identify optimal treatment windows in a mouse model during the formation of HS.

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Anne-Ségolène Cottereau, Irene Buvat, Salim Kanoun, Annibale Versari, Olivier Casasnovas, Stephane Chauvie, Jérôme Clerc, Andrea Gallamini, Michel Meignan (2018 Apr 14)

Is there an optimal method for measuring baseline metabolic tumor volume in diffuse large B cell lymphoma?

European journal of nuclear medicine and molecular imaging : 1463-1464 : DOI : 10.1007/s00259-018-4005-4 En savoir plus
Résumé

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Jessica Goya-Outi, Fanny Orlhac, Raphael Calmon, Agusti Alentorn, Christophe Nioche, Cathy Philippe, Stéphanie Puget, Nathalie Boddaert, Irène Buvat, Jacques Grill, Vincent Frouin, Frederique Frouin (2018 Apr 11)

Computation of reliable textural indices from multimodal brain MRI: suggestions based on a study of patients with diffuse intrinsic pontine glioma.

Physics in medicine and biology : 105003 : DOI : 10.1088/1361-6560/aabd21 En savoir plus
Résumé

Few methodological studies regarding widely used textural indices robustness in MRI have been reported. In this context, this study aims to propose some rules to compute reliable textural indices from multimodal 3D brain MRI. Diagnosis and post-biopsy MR scans including T1, post-contrast T1, T2 and FLAIR images from thirty children with diffuse intrinsic pontine glioma (DIPG) were considered. The hybrid white stripe method was adapted to standardize MR intensities. Sixty textural indices were then computed for each modality in different regions of interest (ROI), including tumor and white matter (WM). Three types of intensity binning were compared [Formula: see text]: constant bin width and relative bounds; [Formula: see text] constant number of bins and relative bounds; [Formula: see text] constant number of bins and absolute bounds. The impact of the volume of the region was also tested within the WM. First, the mean Hellinger distance between patient-based intensity distributions decreased by a factor greater than 10 in WM and greater than 2.5 in gray matter after standardization. Regarding the binning strategy, the ranking of patients was highly correlated for 188/240 features when comparing [Formula: see text] with [Formula: see text], but for only 20 when comparing [Formula: see text] with [Formula: see text], and nine when comparing [Formula: see text] with [Formula: see text]. Furthermore, when using [Formula: see text] or [Formula: see text] texture indices reflected tumor heterogeneity as assessed visually by experts. Last, 41 features presented statistically significant differences between contralateral WM regions when ROI size slightly varies across patients, and none when using ROI of the same size. For regions with similar size, 224 features were significantly different between WM and tumor. Valuable information from texture indices can be biased by methodological choices. Recommendations are to standardize intensities in MR brain volumes, to use intensity binning with constant bin width, and to define regions with the same volumes to get reliable textural indices.

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Fanny Orlhac, Sarah Boughdad, Cathy Philippe, Hugo Stalla-Bourdillon, Christophe Nioche, Laurence Champion, Michaël Soussan, Frédérique Frouin, Vincent Frouin, Irène Buvat (2018 Jan 6)

A Postreconstruction Harmonization Method for Multicenter Radiomic Studies in PET.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine : 1321-1328 : DOI : 10.2967/jnumed.117.199935 En savoir plus
Résumé

Several reports have shown that radiomic features are affected by acquisition and reconstruction parameters, thus hampering multicenter studies. We propose a method that, by removing the center effect while preserving patient-specific effects, standardizes features measured from PET images obtained using different imaging protocols. Pretreatment F-FDG PET images of patients with breast cancer were included. In one nuclear medicine department (department A), 63 patients were scanned on a time-of-flight PET/CT scanner, and 16 lesions were triple-negative (TN). In another nuclear medicine department (department B), 74 patients underwent PET/CT on a different brand of scanner and a different reconstruction protocol, and 15 lesions were TN. The images from department A were smoothed using a gaussian filter to mimic data from a third department (department A-S). The primary lesion was segmented to obtain a lesion volume of interest (VOI), and a spheric VOI was set in healthy liver tissue. Three SUVs and 6 textural features were computed in all VOIs. A harmonization method initially described for genomic data was used to estimate the department effect based on the observed feature values. Feature distributions in each department were compared before and after harmonization. In healthy liver tissue, the distributions significantly differed for 4 of 9 features between departments A and B and for 6 of 9 between departments A and A-S ( < 0.05, Wilcoxon test). After harmonization, none of the 9 feature distributions significantly differed between 2 departments ( > 0.1). The same trend was observed in lesions, with a realignment of feature distributions between the departments after harmonization. Identification of TN lesions was largely enhanced after harmonization when the cutoffs were determined on data from one department and applied to data from the other department. The proposed harmonization method is efficient at removing the multicenter effect for textural features and SUVs. The method is easy to use, retains biologic variations not related to a center effect, and does not require any feature recalculation. Such harmonization allows for multicenter studies and for external validation of radiomic models or cutoffs and should facilitate the use of radiomic models in clinical practice.

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Année de publication : 2017

Florentin Kucharczak, Kevin Loquin, Irène Buvat, Olivier Strauss, Denis Mariano-Goulart (2017 Dec 2)

Interval-based reconstruction for uncertainty quantification in PET.

Physics in medicine and biology : 035014 : DOI : 10.1088/1361-6560/aa9ea6 En savoir plus
Résumé

A new directed interval-based tomographic reconstruction algorithm, called non-additive interval based expectation maximization (NIBEM) is presented. It uses non-additive modeling of the forward operator that provides intervals instead of single-valued projections. The detailed approach is an extension of the maximum likelihood-expectation maximization algorithm based on intervals. The main motivation for this extension is that the resulting intervals have appealing properties for estimating the statistical uncertainty associated with the reconstructed activity values. After reviewing previously published theoretical concepts related to interval-based projectors, this paper describes the NIBEM algorithm and gives examples that highlight the properties and advantages of this interval valued reconstruction.

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Wadad Saba, Sébastien Goutal, Sylvain Auvity, Bertrand Kuhnast, Christine Coulon, Virginie Kouyoumdjian, Irène Buvat, Claire Leroy, Nicolas Tournier (2017 Sep 26)

Imaging the neuroimmune response to alcohol exposure in adolescent baboons: a TSPO PET study using F-DPA-714.

Addiction biology : 1000-1009 : DOI : 10.1111/adb.12548 En savoir plus
Résumé

The effects of acute alcohol exposure to the central nervous system are hypothesized to involve the innate immune system. The neuroimmune response to an initial and acute alcohol exposure was investigated using translocator protein 18 kDa (TSPO) PET imaging, a non-invasive marker of glial activation, in adolescent baboons. Three different alcohol-naive adolescent baboons (3-4 years old, 9 to 14 kg) underwent F-DPA-714 PET experiments before, during and 7-12 months after this initial alcohol exposure (0.7-1.0 g/l). The brain distribution of F-DPA-714 (V ; in ml/cm ) was estimated in several brain regions using the Logan plot analysis and the metabolite-corrected arterial input function. Compared with alcohol-naive animals (V  = 3.7 ± 0.7 ml/cm ), the regional V s of F-DPA-714 were significantly increased during alcohol exposure (V  = 7.2 ± 0.4 ml/cm ; p < 0.001). Regional V s estimated several months after alcohol exposure (V  = 5.7 ± 1.4 ml/cm ) were lower (p < 0.001) than those measured during alcohol exposure, but remained significantly higher (p < 0.001) than in alcohol-naive animals. The acute and long-term effects of ethanol exposure were observed globally across all brain regions. Acute alcohol exposure increased the binding of F-DPA-714 to the brain in a non-human primate model of alcohol exposure that reflects the ‘binge drinking’ situation in adolescent individuals. The effect persisted for several months, suggesting a ‘priming’ of glial cell function after initial alcohol exposure.

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Antoine Schernberg, Sylvain Reuze, Fanny Orlhac, Irène Buvat, Laurent Dercle, Roger Sun, Elaine Limkin, Alexandre Escande, Christine Haie-Meder, Eric Deutsch, Cyrus Chargari, Charlotte Robert (2017 Sep 17)

A score combining baseline neutrophilia and primary tumor SUV measured from FDG PET is associated with outcome in locally advanced cervical cancer.

European journal of nuclear medicine and molecular imaging : 187-195 : DOI : 10.1007/s00259-017-3824-z En savoir plus
Résumé

We investigated whether a score combining baseline neutrophilia and a PET biomarker could predict outcome in patients with locally advanced cervical cancer (LACC).

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