Yolande Petegnief

Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis

The purpose of this study was to assess the prognostic value of early 18F-FDG PET using standardized uptake value (SUV) compared with visual analysis in patients with diffuse large B-cell lymphoma (DLBCL). Methods: Ninety-two patients with newly diagnosed DLBCL underwent 18F-FDG PET prospectively before and after 2 cycles of chemotherapy (at midtherapy). Maximum SUV (SUVmax) and mean SUV (SUVmean) normalized to body weight and body surface area, as well as tumor-to-normal ratios, were computed on the most intense uptake areas. The SUVs, tumor-to-normal ratios, and their changes over time were compared with visual analysis for predicting event-free survival (EFS) and overall survival, using receiver-operating-characteristic (ROC) analysis. Survival curves were estimated with Kaplan–Meier analysis and compared using the log-rank test. Results: With visual analysis, the accuracy of early PET to predict EFS was 65.2%. The 2-y estimate for EFS was 51% (95% confidence interval [CI], 34%–68%) in the PET-positive group compared with 79% (95% CI, 68%–90%) in the PET-negative group (P = 0.009). An optimal cutoff value of 65.7% SUVmax reduction from baseline to midtherapy obtained from ROC analysis yielded an accuracy of 76.1% to predict EFS. The 2-y estimate for EFS was 21% (95% CI, 0%–42%) in patients with SUVmax reduction ≤ 65.7% compared with 79% (95% CI, 69%–88%) in those with reduction > 65.7% (P < 0.0001). Fourteen patients considered as positive on visual analysis could have been reclassified as good responders. Conclusion: SUV-based assessment of therapeutic response during first-line chemotherapy improves the prognostic value of early 18F-FDG PET compared with visual analysis in DLBCL.

Activity and diffusion of tigecycline (GAR-936) in experimental enterococcal endocarditis

ABSTRACT The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in vitro and in experimental endocarditis due to the susceptible Enterococcus faecalis JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA type strain, E. faecium HB217 resistant to tetracycline. MICs of GAR-936 were 0.06 μg/ml for the three strains. In vitro pharmacodynamic studies demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by increasing concentrations to more than 1 μg/ml and a postantibiotic effect ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous injection of [14C]GAR-936 to five rabbits with enterococcal endocarditis sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower clearance of GAR-936 from aortic vegetations than from serum and a homogeneous diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936 (14 mg/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was bacteriostatic against both strains of E. faecalis. Against E. faecium HB217, bacterial counts in vegetations significantly decreased during therapy (P < 0.01), and the effect was similar with GAR-936 at 14 mg/kg b.i.d., 14 mg/kg once a day (o.d.), and 7 mg/kg o.d., which provided concentrations in serum constantly above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR-936-resistant mutants were selected in vivo with any regimen. We concluded that the combination of prolonged half-life, significant postantibiotic effect, and good and homogeneous diffusion into the vegetations may account for the in vivo activity of GAR-936 against enterococci susceptible or resistant to glycopeptides and tetracyclines, even when using a o.d. regimen in rabbits.

Quantitative autoradiography using a radioimager based on a multiwire proportional chamber.

Determination of the biodistribution of radiopharmaceuticals is an important issue for the evaluation of their performance in diagnosis and therapy. In this study, we evaluated a digital radioimager (RI) based on a multiwire proportional chamber for quantitative autoradiography (AR). The RI allows direct detection of electronic emissions of gamma emitters. Its qualitative and quantitative performances were tested on 99mTc and (111)In labelled sections and compared with conventional film AR. Linearity of count rate versus activity was verified over a 104 range of activity. As compared with film AR, a substantial improvement of the detection limit was obtained even for acquisition periods up to 20 times less than film exposure times. We provided the basis for quantitative analysis with tissue equivalent paste standards: the 99mTc and (111)In RI counting efficiencies were respectively 1.19% and 2.35%. We illustrated the respective values of RI and film AR in two rat studies: 99mTc-DMSA in kidney and dual-isotope 99mTc-MIBI and (111)In-antimyosin in heart. Calculated activity concentrations on sections of rat organs confirmed good correlation to gamma counting (deviation less than 12%). We suggest RI as a convenient technique for fast localization of single or dual-isotope tracers and determination of activity distribution.

Full modelling of the MOSAIC animal PET system based on the GATE Monte Carlo simulation code

Positron emission tomography (PET) systems dedicated to animal imaging are now widely used for biological studies. The scanner performance strongly depends on the design and the characteristics of the system. Many parameters must be optimized like the dimensions and type of crystals, geometry and field-of-view (FOV), sampling, electronics, lightguide, shielding, etc. Monte Carlo modelling is a powerful tool to study the effect of each of these parameters on the basis of realistic simulated data. Performance assessment in terms of spatial resolution, count rates, scatter fraction and sensitivity is an important prerequisite before the model can be used instead of real data for a reliable description of the system response function or for optimization of reconstruction algorithms. The aim of this study is to model the performance of the Philips Mosaic animal PET system using a comprehensive PET simulation code in order to understand and describe the origin of important factors that influence image quality. We use GATE, a Monte Carlo simulation toolkit for a realistic description of the ring PET model, the detectors, shielding, cap, electronic processing and dead times. We incorporate new features to adjust signal processing to the Anger logic underlying the Mosaic system. Special attention was paid to dead time and energy spectra descriptions. Sorting of simulated events in a list mode format similar to the system outputs was developed to compare experimental and simulated sensitivity and scatter fractions for different energy thresholds using various models of phantoms describing rat and mouse geometries. Count rates were compared for both cylindrical homogeneous phantoms. Simulated spatial resolution was fitted to experimental data for (18)F point sources at different locations within the FOV with an analytical blurring function for electronic processing effects. Simulated and measured sensitivities differed by less than 3%, while scatter fractions agreed within 9%. For a 410-665 keV energy window, the measured sensitivity for a centred point source was 1.53% and mouse and rat scatter fractions were respectively 12.0% and 18.3%. The scattered photons produced outside the rat and mouse phantoms contributed to 24% and 36% of total simulated scattered coincidences. Simulated and measured single and prompt count rates agreed well for activities up to the electronic saturation at 110 MBq for the mouse and rat phantoms. Volumetric spatial resolution was 17.6 microL at the centre of the FOV with differences less than 6% between experimental and simulated spatial resolution values. The comprehensive evaluation of the Monte Carlo modelling of the Mosaic system demonstrates that the GATE package is adequately versatile and appropriate to accurately describe the response of an Anger logic based animal PET system.

[F-18]-Fluoro-2-deoxy-d-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murine B cell lymphoma model

Abstract[F-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a non-invasive imaging technique which has recently been validated for the assessment of therapy response in patients with aggressive non-Hodgkin’s lymphoma. Our objective was to determine its value for the evaluation of immunotherapy efficacy in immunocompetent Balb/c mice injected with the A20 syngeneic B lymphoma cell line. The high level of in vitro FDG uptake by A20 cells validated the model for further imaging studies. When injected intravenously, the tumour developed as nodular lesions mostly in liver and spleen, thus mimicking the natural course of an aggressive human lymphoma. FDG-PET provided three-dimensionnal images of tumour extension including non-palpable lesions, in good correlation with ex vivo macroscopic examination. When mice were pre-immunized with an A20 cell lysate in adjuvant before tumour challenge, their significantly longer survival, compared to control mice, were associated with a lower incidence of lymphoma visualized by PET at different time points. Estimation of tumour growth and metabolism using the calculated tumour volumes and maximum standardized uptake values, respectively, also demonstrated delayed lymphoma development and lower activity in the vaccinated mice. Thus, FDG-PET is a sensitive tool relevant for early detection and follow-up of internal tumours, allowing discrimination between treated and non-treated small animal cohorts without invasive intervention.

Cardiac gated equilibrium radionuclide angiography and multiharmonic Fourier phase analysis: Optimal acquisition parameters in arrhythmogenic right ventricular cardiomyopathy

BackgroundMultiharmonic Fourier phase analysis of radionuclide angiography is a well-established method for the diagnosis of arrhythmogenic right ventricular cardiomyopathy. We sought to determine the optimal acquisition parameters: number of frames per cycle and number of counts per frame, with all other acquisition and processing parameters being fixed.Methods and ResultsRadionuclide angiography with list mode acquisition was performed in 10 normal subjects (pilot group) and 11 patients with arrhythmogenic right ventricular cardiomyopathy (validation group), allowing the reconstruction of electrocardiography-gated constant phase studies with different parameters: 16, 24, and 32 frames per cycle and 200, 400, 600, and 800 kcounts per frame. Three harmonics Fourier phase analysis was applied, and optimal acquisition parameters (defined as those providing best homogeneous phase distribution histogram in the pilot group) were defined as judged by the H3 right ventricular phase SD and Δ 95%. These were 16 frames per cycle and 600 kcounts per frame. Then we verified in the validation group that these optimal acquisition parameters did not induce any significant relative loss of information compared with other acquisition parameters with more temporal resolution (24 and 32 frames per cycle) or more statistics (800 kcounts per frame). This result was realized by the calculation of normalized H3 right ventricular SD, right ventricular Δ 95%, and (SD[left ventricle]-SD[right ventricle]).ConclusionsIn practice, 16 frames per cycle and 600 kcounts per frame are optimal for multiharmonic Fourier phase analysis, with all other acquisition and processing variables being fixed as specified.

Detection of recurrent colorectal carcinoma by 18F-FDG: comparison of the clinical performances of FDG PET and FDG CDET.

ObjectivesTo assess the clinical performance of fluorodeoxyglucose positron emission tomography (FDG PET) using either a coincidence (CDET) gamma camera or PET equipment with NaI crystals for the detection of recurrences of colorectal cancer. MethodsFrom July 1997 to December 1999, 290 examinations were performed in 244 patients using a CDET gamma camera (2-dimensional system with 19 mm thick crystals). Additionally, from January 2000 to July 2002, 354 examinations were performed in 303 patients using PET (3-dimensional system with NaI crystals). ResultsFour hundred and seventy-three of the 644 examinations performed were evaluable on the basis of histological data (202 examinations) or more than 6 months of follow-up (273 examinations). The performances of the two systems were equivalent on a patient basis (sensitivity, specificity and accuracy of dedicated PET was 92%, 84% and 90%, respectively; and sensitivity, specificity and accuracy of CDET was 90%, 94% and 91%, respectively). On a site basis, a highly significant reduction in sensitivity was observed for lesions ≤10 mm vs. >10 mm with both PET and the CDET gamma camera, but no difference was observed between PET and CDET according to the size of the lesions. ConclusionFor detection of recurrent colorectal carcinoma, a 2-D coincidence gamma camera with 19 mm thick crystals and optimized acquisition and reconstruction parameters provides similar results in terms of accuracy, both per patient and per site, to those of an NaI PET camera.

Positron emission tomography with [18F]-FDG in oncology

Abstract Positron Emission Tomography (PET) is a several decade old imaging technique that has more recently demonstrated its utility in clinical applications. The imaging agents used for PET contain a positron emmiter coupled to a molecule that drives the radionuclide to target organs or to tissues performing the targetted biological function. PET is then part of functional imaging. As compared to conventional scintigraphy that uses gamma photons, the coincidence emission of two 511 keV annihilation photons in opposite direction that finally results from by beta plus decay makes it possible for PET to get rid of the collimators that greatly contribute to the poor resolution of scintigraphy. In this article, the authors describe the basics of physics for PET imaging and report on the clinical performances of the most commonly used PET tracer: [ 18 F]-fluorodeoxyglucose (FDG). A recent and promising development in this field is fusion of images coming from different imaging modalities. New PET machines now include a CT and this fusion is therefore much easier.

Determination of left ventricular cardiac volume by simultaneous radionuclide angiography and measurement of oxygen consumption at rest and during maximal exercise: a comparison of two non-invasive isotopic procedures.

The investigation of left ventricular contractile reserve usually requires the determination of left ventricular volume, but its measurement with radionuclide angiography is difficult. The aim of this study was to determine left ventricular volume directly during exercise by the simultaneous measurement of peak exercise left ventricular ejection fraction (LVEF) and oxygen consumption (VO2max) and to compare the results with another geometric method. In the absence of lung disease, the systemic arteriovenous oxygen difference (DAVmax) during maximal exercise converges to 0.13-0.14 ml O2 per ml blood. The measurement of VO2max allows maximal cardiac output (COmax) to be calculated as VO2max = COmax. DAVmax. By simultaneously determining LVEFex, exercise end-diastolic volume (EDVex) can then be expressed as a linear function of VO2max, maximal heart rate (HRmax), DAVmax and LVEFex. Then, the relationship between end-diastolic counts and true volume can be derived at rest. The two methods were closely correlated (r = 0.91, P < 0.001), despite the geometric method being less accurate when applied to low counting statistic acquisitions. We conclude that rest and exercise left ventricular volume can be determined non-invasively by the simultaneous measurement of VO2max and LVEFex. Furthermore, this method provides additional prognostic information which is clinically relevant in the staging of patients with heart failure.