Biomedical subjects

Philippe Gervais

Publications and source records attributed to Philippe Gervais.

5 recordsLinked to original sources

PubMed2005

Biodistribution and radiation dosimetry of [11C]raclopride in healthy volunteers.

PURPOSE: This study reports on the whole-body biodistribution and radiation dosimetry of [11C]raclopride, a dopamine D2 receptor antagonist. METHODS: In three healthy male volunteers, whole-body scans were performed up to 2 h following i.v. injection of 320+/-65 MBq [11C]raclopride. Transmission scans (3 min per step, eight or nine steps according to the height of the subject) in 2D mode were used for subsequent attenuation correction of emission scans. Emission scans (1 min per step, eight or nine steps) were acquired over 2 h. Venous blood samples and urine were collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, lungs, kidneys and liver was fitted to a mono-exponential model, as an uptake phase followed by a mono-exponential washout, for urinary bladder to generate time-activity curves. Using the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses. RESULTS: Blood pressure and ECG findings remained unchanged after tracer injection. The analysed blood and urine pharmacological parameters did not change significantly after [(11)C]raclopride injection. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the gall-bladder, kidneys and liver. High activity was observed in the gall-bladder during the whole study. The kidneys, urinary bladder wall, liver and gall-bladder received the highest absorbed doses. The average effective dose of [11C]raclopride was estimated to be 6.7+/-0.4 microSv/MBq. CONCLUSION: The amount of [11C]raclopride required for adequate dopamine D2 receptor imaging results in an acceptable effective dose equivalent, permitting two or three repeated clinical PET imaging studies, with the injection of 222 MBq for each study.

Adult↗

PubMed2005

Glycolysis versus TCA cycle in the primate brain as measured by combining 18F-FDG PET and 13C-NMR.

The glycolytic flux (cerebral metabolic rate of glucose CMRglc) and the TCA cycle flux (VTCA) were measured in the same monkeys by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 13C NMR spectroscopy, respectively. Registration of nuclear magnetic resonance (NMR) and PET data were used for comparison of CMRglc and VTCA in the exact same area of the brain. Both fluxes were in good agreement with literature values (CMRglc=0.23+/-0.03 micromol/g min, VTCA=0.53+/-0.13 micromol/g min). The resulting [CMRglc/VTCA] ratio was 0.46+/-0.12 (n=5, mean+/-s.d.), not significantly different from the 0.5 expected when glucose is the sole fuel that is completely oxidized. Our results provide a cross-validation of both techniques. Comparison of CMRglc with VTCA is in agreement with a metabolic coupling between the TCA cycle and glycolysis under normal physiologic conditions.

Animals↗

PubMed2004

Engagement of ICAM-3 provides a costimulatory signal for human immunodeficiency virus type 1 replication in both activated and quiescent CD4+ T lymphocytes: implications for virus pathogenesis.

Human immunodeficiency virus type 1 (HIV-1) replication is regulated by several extracellular signals. We demonstrate that intercellular adhesion molecule 3 (ICAM-3) acts as a costimulating molecule to increase HIV-1 transcription and viral production, a process allowing productive infection of quiescent CD4+ T lymphocytes. The present work suggests an important role for ICAM-3 in HIV-1 replication.

Antigens, CD↗

PubMed2004

Arterial input function measurement without blood sampling using a beta-microprobe in rats.

UNLABELLED: The evaluation of every new radiotracer involves pharmacokinetic studies on small animals to determine its biodistribution and local kinetics. To extract relevant biochemical information, time-activity curves for the regions of interest are mathematically modeled on the basis of compartmental models that require knowledge of the time course of the tracer concentration in plasma. Such a time-activity curve, usually termed input function, is determined in small animals by repeated blood sampling and subsequent counting in a well counter. The aim of the present work was to propose an alternative to blood sampling in small animals, since this procedure is labor intensive, exposes the staff to radiation, and leads to an important loss of blood, which affects hematologic parameters. METHODS: Monte Carlo simulations were performed to evaluate the feasibility of measuring the arterial input function using a positron-sensitive microprobe placed in the femoral artery of a rat. The simulation results showed that a second probe inserted above the artery was necessary to allow proper subtraction of the background signal arising from tracer accumulation in surrounding tissues. This approach was then validated in vivo in 5 anesthetized rats. In a second set of experiments, on 3 rats, a third probe was used to simultaneously determine 18F-FDG accumulation in the striatum. RESULTS: The high temporal resolution of the technique allowed accurate determination of the input function peak after bolus injection of 18F-FDG. Quantitative input functions were obtained after normalization of the arterial time-activity curve for a late blood sample. In the second set of experiments, compartmental modeling was achieved using either the blood samples or the microprobe data as the input function, and similar kinetic constants were found in both cases. CONCLUSION: Although direct quantification proved difficult, the microprobe allowed accurate measurement of arterial input function with a high temporal resolution and no blood loss. The technique, because offering adequate sensitivity and temporal resolution for kinetic measurements of radiotracers in the blood compartment, should facilitate quantitative modeling for radiotracer studies in small animals.

Algorithms↗

PubMed2002

In vivo quantification of localized neuronal activation and inhibition in the rat brain using a dedicated high temporal-resolution beta +-sensitive microprobe.

Understanding brain disorders, the neural processes implicated in cognitive functions and their alterations in neurodegenerative pathologies, or testing new therapies for these diseases would benefit greatly from combined use of an increasing number of rodent models and neuroimaging methods specifically adapted to the rodent brain. Besides magnetic resonance (MR) imaging and functional MR, positron-emission tomography (PET) remains a unique methodology to study in vivo brain processes. However, current high spatial-resolution tomographs suffer from several technical limitations such as high cost, low sensitivity, and the need of restraining the animal during image acquisition. We have developed a beta(+)-sensitive high temporal-resolution system that overcomes these problems and allows the in vivo quantification of cerebral biochemical processes in rodents. This beta-MICROPROBE is an in situ technique involving the insertion of a fine probe into brain tissue in a way very similar to that used for microdialysis and cell electrode recordings. In this respect, it provides information on molecular interactions and pathways, which is complementary to that produced by these technologies as well as other modalities such as MR or fluorescence imaging. This study describes two experiments that provide a proof of concept to substantiate the potential of this technique and demonstrate the feasibility of quantifying brain activation or metabolic depression in individual living rats with 2-[(18)F]fluoro-2-deoxy-d-glucose and standard compartmental modeling techniques. Furthermore, it was possible to identify correctly the origin of variations in glucose consumption at the hexokinase level, which demonstrate the strength of the method and its adequacy for in vivo quantitative metabolic studies in small animals.

Animals↗