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Jean-Robert Deverre

Publications and source records attributed to Jean-Robert Deverre.

7 recordsLinked to original sources
PubMed2006

Predicting plutonium decorporation efficacy after intravenous administration of DTPA formulations: Study of pharmacokinetic-pharmacodynamic relationships in rats.

PURPOSE: The objectives of this study were: 1) to assess the relationship between plutonium decorporation (increased excretion and reduced retention in main organs of deposition) induced by intravenous liposome formulations of the chelating agent diethylene triamine pentaacetic acid (DTPA) and its pharmacokinetics, and 2) to model the renal excretion of plutonium after treatment with liposome-encapsulated DTPA in order to predict its efficacy and to optimise treatment schedules. MATERIALS AND METHODS: Pharmacokinetic parameters from plasma or urinary data (days 0-16 sample collections) were modelled versus decorporation efficacy, and best correlations were selected for their goodness of fit. RESULTS: The plutonium decorporation enhancement by DTPA liposomal formulations was well described by logistic models and the best correlation was observed with the area under the DTPA concentration curve of each formulation. The plutonium urinary excretion rates decreased mono-exponentially as a function of time after a single dose and the proposed model allowed a simple determination of the elimination half-life of the Pu-DTPA complex, a reasonably good approximation of the long-term efficacy of the treatments from truncated urinary data. CONCLUSIONS: Both liposomal formulations of chelating agents and pharmacokinetic approaches to plutonium decorporation should be helpful in optimising treatment protocols.

Animals↗
PubMed2005

Pharmacokinetics of DTPA entrapped in conventional and long-circulating liposomes of different size for plutonium decorporation.

The aim of the present study was to develop an efficient DTPA liposome formulation designed for plutonium decorporation. DTPA was encapsulated in conventional (CL) and polyethylene glycol-coated stealth liposomes (SL) prepared by extrusion followed by the freeze-thawing method and sizing from around 100 to 800 nm. DTPA encapsulation percentages were approximately 30% in CL of any size but dropped from 48% to 7% as the diameter of SL was reduced. The pharmacokinetics of [(14)C]-DTPA encapsulated in large and small vesicles was evaluated in rats after a single intravenous administration. Both liposomal composition and size reduction had a significant impact on pharmacokinetic parameters, inducing a marked increased in exposure of the body to DTPA and its delayed excretion. DTPA distribution was moderate in liver but enhanced in spleen and bone and was dose-dependent, especially when SL of 100 nm were given. In conclusion, small and stealth(R) vesicles have interesting properties in delivering DTPA to contaminated tissues.

Animals↗
PubMed2005

In vivo imaging of human cerebral nicotinic acetylcholine receptors with 2-18F-fluoro-A-85380 and PET.

UNLABELLED: 2-(18)F-fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-(18)F-fluoro-A-85380) is a PET radioligand that is specific for nicotinic acetylcholine receptors (nAChRs) and has a high affinity for the alpha(4)beta(2) subtype. The purpose of this study was to evaluate different strategies to quantify 2-(18)F-fluoro-A-85380 binding in healthy nonsmoking human volunteers. METHODS: After intravenous injection of 189 +/- 30 MBq (0.8-5.7 nmol) of 2-(18)F-fluoro-A-85380, the first dynamic PET scan was acquired over 150 min. The second 30-min PET scan was performed 60 min later. Time-activity curves were generated from volumes of interest. 2-(18)F-Fluoro-A-85380 volume of distribution (DV) was quantified using compartmental kinetic analysis and Logan graphical analysis. In the kinetic analysis, the 1-tissue compartment model (1TCM) and the 2-tissue (2TCM) compartment model were applied. The most appropriate kinetic model was determined using the Akaike Information Criterion. The effect of reducing the PET study duration on the reliability of the DV values computed by the kinetic and the graphical analyses was evaluated. RESULTS: Time-activity curves were better described by the 2TCM. The DV values ranged from 5.2 +/- 0.5 in the occipital cortex, 6.2 +/- 0.2 in the frontal cortex, and 7.3 +/- 0.4 in the putamen to 15.4 +/- 2.1 in the thalamus. These regional DV values were consistent with the distribution of nAChRs in the human brain. Logan graphical analysis provided slightly lower DV values than those of the 2TCM (from -3.5% in the occipital cortex to -6.6% in the thalamus). The minimal study duration required to obtain stable DV estimates in all regions was similar for the 2 methods: 140 min for the 2TCM and 150 min for the Logan analysis. DV estimates obtained with the 2TCM were more stable than those calculated by the Logan approach for the same scan duration. CONCLUSION: These results show that 2-(18)F-fluoro-A-85380 can be used to assess nAChRs binding in the human brain with PET.

Adult↗
PubMed2002

Anti-cancer drug diffusion within living rat brain tissue: an experimental study using [3H](6)-5-fluorouracil-loaded PLGA microspheres.

This study was performed (i) to monitor the diffusion of the anti-cancer drug 5-fluorouracil (5-FU) and (ii) to elucidate the fate of poly(lactide-co-glycolide) (PLGA) based microspheres within living rat brain tissue upon intracranial implantation. Drug-loaded microparticles were prepared using a solvent emulsion/extraction process and administered into healthy and C6 glioma-bearing Sprague-Dawley rats. The same surgical procedure was carried out with magnetite-loaded microspheres. To monitor 5-FU diffusion from the implantation site, tissue combustion was performed on animals implanted with tritiated drug microspheres. T2-weighted nuclear magnetic resonance imaging was undertaken on animals implanted with magnetite-loaded microspheres to determine microsphere localization after deposit. Results show that an important microparticle backflow occurs in healthy rats, whereas the microspheres remain at the site of administration in C6 glioma-bearing rats. Drug diffusion is limited to the vicinity of the implantation site.

Animals↗
PubMedDate not supplied

Early detection of chemoresistance in vivo through the use of a radiolabeled antisense oligonucleotide.

AIMS: Radiolabeled antisense oligonucleotide to target the mRNA of the hmdr1 gene for diagnostic purposes is a new concept for evaluating the chemoresistance of tumors in vivo. METHODS AND RESULTS: An 18 mer complementary to the zone which contains the translation initiation codon of the hmdr1 gene was modified using one phosphoramidate group and one dimethoxytrityle group at the 5' and 3'ends. It permitted probe radiolabeling by 125I. Chemical modifications made to the antisense probe ensured the stability in biological media tested by incubation with human serum at 37 degrees C from 5 minutes to 24 hours. These modifications did not interfere with recognition of the target. Retention of the antisense probe followed the expression level of the target transcript in in vitro and in vivo studies. In vitro, after a 2-hour incubation in the presence of K562--sensitive (S) and- resistant (R) cell lines, uptake was respectively 4.27 +/- 0.96% ID/mg protein and 7.78 +/- 0.46% ID/mg protein (p < 0.001). In vivo, the ratios between radioactivity found in the tumor and that found in the striated muscle and in the blood were, respectively, 20 and 3 for IGR OV1 resistant tumor and 1 and 0.3 for the sensitive one. CONCLUSION: In our study, resistant cell lines and tumor showed greater retention of the specific probe than the sensitive ones. This constitutes a further advance towards non invasive imaging of resistant genes involved in chemoresistance. These results are encouraging: the current trend in innovative cancer therapy is moving towards targeting the genes of interest.

ATP Binding Cassette Transporter, Subfamily B, Mem↗