Value of positron emission tomography in full-thickness chest wall resections for malignancies

Rapport de synthèse : Les tumeurs de la paroi thoracique sont des pathologies graves dont le traitement principal consiste en une résection chirurgicale. L'enjeu majeur de cette intervention ontologique est de réséquer la totalité de la tumeur, ce qui nécessite une planification préopératoire minutieuse. Classiquement, l'identification et la localisation de la tumeur se fait à l'aide de la tomodensitométrie (computed tomography, CT) ou de l'imagerie par résonnance magnétique (1RM). Actuellement, l'imagerie nucléaire fonctionnelle par tomographie par émission de positons (positron emission tomography, PET) qui peut être couplée au CT (PET/CT) est de plus en plus appliquée aux patients présentant une tumeur maligne. Son efficacité a fréquemment été démontrée. Le but de la présente étude est d'évaluer la valeur du PET dans la planification de la résection des tumeurs de la paroi thoracique. Une analyse rétrospective de dix-huit patients opérés entre 2004 et 2006 a été réalisée; Dans ce groupe de patient, la taille de la tumeur mesurée sur la pièce opératoire réséquée a été comparée à la taille de la tumeur mesurée sur le CT et le PET. Les résultats démontrent que le CT surestimait de manière consistante la taille réelle de la tumeur par rapport au PET (+64% par rapport à +1%, P<0.001). De plus, le PET s'est avéré particulièrement performant pour prédire la taille des tumeurs de plus de 5.5 cm de diamètre par rapport au CT (valeur prédictive positive 80% par rapport à 44% et spécificité 93% par apport à 64%, respectivement). Cette étude démontre que le PET permettrait de mesurer la taille des tumeurs de la paroi thoracique de manière plus précise que le CT. Cette nouvelle modalité diagnostique s'avèrerait donc utile pour planifier les résections chirurgicales de telles tumeurs. A notre connaissance, aucune publication ne décrit la valeur du PET dans ce domaine. Les performances accrues du PET permettraient une meilleure délimitation des tumeurs ce qui améliorerait la précision de la résection chirurgicale. En conclusion, cette étude préliminaire rétrospective démontre la faisabilité du PET pour les tumeurs de la paroi thoracique. Ces résultats devraient être confirmés par une étude prospective incluant un plus grand nombre de patients avec la perspective de juger l'impact clinique réel du PET sur la prise en charge thérapeutique des patients.

Study of common database feeding with results coming from different analytical methods in the framework of illicit drugs chemical profiling

Analytical results harmonisation is investigated in this study to provide an alternative to the restrictive approach of analytical methods harmonisation which is recommended nowadays for making possible the exchange of information and then for supporting the fight against illicit drugs trafficking. Indeed, the main goal of this study is to demonstrate that a common database can be fed by a range of different analytical methods, whatever the differences in levels of analytical parameters between these latter ones. For this purpose, a methodology making possible the estimation and even the optimisation of results similarity coming from different analytical methods was then developed. In particular, the possibility to introduce chemical profiles obtained with Fast GC-FID in a GC-MS database is studied in this paper. By the use of the methodology, the similarity of results coming from different analytical methods can be objectively assessed and the utility in practice of database sharing by these methods can be evaluated, depending on profiling purposes (evidential vs. operational perspective tool). This methodology can be regarded as a relevant approach for database feeding by different analytical methods and puts in doubt the necessity to analyse all illicit drugs seizures in one single laboratory or to implement analytical methods harmonisation in each participating laboratory.

Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

Purification of recombinant proteins by chemical removal of the affinity tag.

The efficient removal of a N- or C-terminal purification tag from a fusion protein is necessary to obtain a protein in a pure and active form, ready for use in human or animal medicine. Current techniques based on enzymatic cleavage are expensive and result in the presence of additional amino acids at either end of the proteins, as well as contaminating proteases in the preparation. Here we evaluate an alternative method to the one-step affinity/protease purification process for large-scale purification. It is based upon the cyanogen bromide (CNBr) cleavage at a single methionine placed in between a histidine tag and a Plasmodium falciparum antigen. The C-terminal segment of the circumsporozoite polypeptide was expressed as a fusion protein with a histidine tag in Escherichia coli purified by Ni-NAT agarose column chromatography and subsequently cleaved by CNBr to obtain a polypeptide without any extraneous amino acids derived from the cleavage site or from the affinity purification tag. Thus, a recombinant protein is produced without the need for further purification, demonstrating that CNBr cleavage is a precise, efficient, and low-cost alternative to enzymatic digestion, and can be applied to large-scale preparations of recombinant proteins.

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water.

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.

Diagnostic performance of &supl;⁸F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to conduct a systematic review and perform a meta-analysis on the diagnostic performances of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for giant cell arteritis (GCA), with or without polymyalgia rheumatica (PMR). METHODS: MEDLINE, Embase and the Cochrane Library were searched for articles in English that evaluated FDG PET in GCA or PMR. All complete studies were reviewed and qualitatively analysed. Studies that fulfilled the three following criteria were included in a meta-analysis: (1) FDG PET used as a diagnostic tool for GCA and PMR; (2) American College of Rheumatology and Healey criteria used as the reference standard for the diagnosis of GCA and PMR, respectively; and (3) the use of a control group. RESULTS: We found 14 complete articles. A smooth linear or long segmental pattern of FDG uptake in the aorta and its main branches seems to be a characteristic pattern of GCA. Vessel uptake that was superior to liver uptake was considered an efficient marker for vasculitis. The meta-analysis of six selected studies (101 vasculitis and 182 controls) provided the following results: sensitivity 0.80 [95% confidence interval (CI) 0.63-0.91], specificity 0.89 (95% CI 0.78-0.94), positive predictive value 0.85 (95% CI 0.62-0.95), negative predictive value 0.88 (95% CI 0.72-0.95), positive likelihood ratio 6.73 (95% CI 3.55-12.77), negative likelihood ratio 0.25 (95% CI 0.13-0.46) and accuracy 0.84 (95% CI 0.76-0.90). CONCLUSION: We found overall valuable diagnostic performances for FDG PET against reference criteria. Standardized FDG uptake criteria are needed to optimize these diagnostic performances.

Radioimmuno positron emission tomography with monoclonal antibodies: a new approach to quantifying in vivo tumour concentration and biodistribution for radioimmunotherapy.

Radioimmunodetection of tumours with monoclonal antibodies is becoming an established procedure. Positron emission tomography (PET) shows better resolution than normal gamma camera single photon emission tomography and can provide more precise quantitative data. Thus, in the present study, these powerful methods have been combined to perform radioimmuno PET (RI-PET). Monoclonal antibodies directed against carcinoembryonic antigen (CEA) an IgG, its F(ab')2 and a mouse-human chimeric IgG derived from it were labelled with 124I, a positron-emitting radionuclide with a convenient physical half-life of four days. Mice, xenografted with a CEA-producing human colon carcinoma, were injected with the 124I-MAb and the tumours were visualized using PET. The concentrations of 124I in tumour and normal tissue were determined by both PET and direct radioactivity counting of the dissected animals, with very good agreement. To allow PET quantification, a procedure was established to account for the presence of radioactivity during the absorption correction measurement (transmission scan). Comparison of PET and tissue counting indicates that this novel combination of radioimmunolocalization and PET (RI-PET) will provide, in addition to more precise diagnosis, more accurate radiation dosimetry for radioimmunotherapy.

Ictal cerebral positron emission tomography (PET) in focal status epilepticus.

The diagnosis of focal status epilepticus (SE) can be challenging, particularly when clinical manifestations leave doubts about its nature, and electroencephalography (EEG) is not conclusive. This work addresses the utility of ictal (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in focal SE, which was performed in eight patients in whom SE was finally diagnosed. Clinical, MRI and EEG data were reviewed. (18)F-FDG-PET proved useful: (1) to establish the diagnosis of focal SE, when clinical elements were equivocal or the EEG did not show clear-cut epileptiform abnormalities; (2) to delineate the epileptogenic area in view of possible resective surgery; and (3) when clinical features, MRI and EEG were incongruent regarding the origin of SE. We suggest that ictal (18)F-FDG-PET may represent a valuable diagnostic tool in selected patients with focal SE or frequent focal seizures.

The politics of contaminated sites management : institutional regime change and actor's mode of participation in the environmental management of the Bonfol Chemical Waste Landfill in Switzerland

By the end of the 1970s, contaminated sites had emerged as one of the most complex and urgent environmental issues affecting industrialized countries. The authors show that small and prosperous Switzerland is no exception to the pervasive problem of sites contamination, the legacy of past practices in waste management having left some 38,000 contaminated sites throughout the country. This book outlines the problem, offering evidence that open and polycentric environmental decision-making that includes civil society actors is valuable. They propose an understanding of environmental management of contaminated sites as a political process in which institutions frame interactions between strategic actors pursuing sometimes conflicting interests. In the opening chapter, the authors describe the influences of politics and the power relationships between actors involved in decision-making in contaminated sites management, which they term a "wicked problem." Chapter Two offers a theoretical framework for understanding institutions and the environmental management of contaminated sites. The next five chapters present a detailed case study on environmental management and contaminated sites in Switzerland, focused on the Bonfol Chemical Landfill. The study and analysis covers the establishment of the landfill under the first generation of environmental regulations, its closure and early remediation efforts, and the gambling on the remediation objectives, methods and funding in the first decade of the 21st Century. The concluding chapter discusses the question of whether the strength of environmental regulations, and the type of interactions between public, private, and civil society actors can explain the environmental choices in contaminated sites management. Drawing lessons from research, the authors debate the value of institutional flexibility for dealing with environmental issues such as contaminated sites.

Matters Relating to a Forced Move of, Use of a Chemical Agent on and Withdrawal of Medication for Inmate Craig Gardner, 1994

Case Number 91-151 Craig Gardner, an inmate in the Iowa prison system, was the subject of a force move by correctional officers while incarcerated at the Iowa State Penitentiary (ISP). This action involved the use of a chemical agent. This investigation began as a review of the use of a chemical agent in a forced cell move on June 30, 1991.

Role of Methyl Salicylate on Oviposition Deterrence in Arabidopsis thaliana.

Plants attacked by herbivores have evolved different strategies that fend off their enemies. Insect eggs deposited on leaves have been shown to inhibit further oviposition through visual or chemical cues. In some plant species, the volatile methyl salicylate (MeSA) repels gravid insects but whether it plays the same role in the model species Arabidopsis thaliana is currently unknown. Here we showed that Pieris brassicae butterflies laid fewer eggs on Arabidopsis plants that were next to a MeSA dispenser or on plants with constitutively high MeSA emission than on control plants. Surprisingly, the MeSA biosynthesis mutant bsmt1-1 treated with egg extract was still repellent to butterflies when compared to untreated bsmt1-1. Moreover, the expression of BSMT1 was not enhanced by egg extract treatment but was induced by herbivory. Altogether, these results provide evidence that the deterring activity of eggs on gravid butterflies is independent of MeSA emission in Arabidopsis, and that MeSA might rather serve as a deterrent in plants challenged by feeding larvae.

Nature, evolution and characterisation of rhizospheric chemical exudates affecting root herbivores

Similar to aboveground herbivores, root-feeding insects must locate and identify suitable resources. In the darkness of soil, they mainly rely on root chemical exudations and, therefore, have evolved specific behaviours. Because of their impact on crop yield, most of our knowledge in belowground chemical ecology is biased towards soil-dwelling insect pests. Yet the increasing literature on volatile-mediated interactions in the ground underpins the great importance of chemical signalling in this ecosystem and its potential in pest control. Here, we explore the ecology and physiology of these chemically based interactions. An evolutionary approach reveals interesting patterns in the response of insects to particular classes of volatile or water-soluble organic compounds commonly emitted by roots. Food web analyses reasonably support that volatiles are used as long-range cues whereas water-soluble molecules serve in host acceptance/rejection by the insect; however, data are still scarce. As a case study, the chemical ecology of Diabrotica virgifera virgifera is discussed and applications of belowground signalling in pest management are examined. Soil chemical ecology is an expanding field of research and will certainly be a hub of our understanding of soil communities and subsequently of the management of belowground ecosystem services.

Morphological, chemical and developmental aspects of the Dufour gland in some eusocial bees (Hymenoptera, Apidae): a review

Morphological, chemical and developmental aspects of the Dufour gland in some eusocial bees (Hymenoptera, Apidae): a review. The present revision focused on the more recent data about the Dufour gland in some eusocial bees, taking in account general aspects of its morphology, secretion chemical nature, bio-synthetic pathway and development. Many functions have been attributed to this gland in eusocial bees, but none are convincing. With the new data about this gland, not only the secretion chemical pathway of the Dufour gland may be reasonable understood, as its function in some eusocial bees, especially Apis mellifera Linné, 1758, which has been extensively studied in the last years.