Biomedical subjects

P Hantraye

Publications and source records attributed to P Hantraye.

82 records · Page 5Linked to original sources

PubMed1986

[76Br]bromolisuride: a new tool for quantitative in vivo imaging of D-2 dopamine receptors.

Bromolisuride, an ergoline derivative, was labeled with the positron emitter radionuclide, bromine 76. In vitro and in vivo binding and competition studies in rats demonstrated a high affinity (KD = 0.3 nM) and a high specificity of this new radioligand for D-2 dopamine receptors. PET kinetic studies in baboons showed an accumulation of [76Br]bromolisuride in the striatum which reached a maximum 30 min post-injection and which could be displaced by haloperidol. All these results indicated that this new ligand is certainly suitable for the non-invasive in vivo quantitative imaging of D-2 dopamine receptor sites in human brain.

Animals↗

PubMed1986

Dopaminergic and benzodiazepine receptors studied in vivo by PET.

Using Positron Emission Tomography (PET) and specific radioligands, dopaminergic D2 (DA-D2 receptors) and benzodiazepine receptors (BZ-receptors) were studied in living animals during normal and pathological conditions. In vivo characterization of both receptors was performed using two highly specific antagonists namely: 11C-Ro 15 1788 for BZ-receptors and 76 Br-Bromospiperone for DA-D2 receptors. Changes in 11c-Ro 15 1788 specific binding to BZ-receptors were observed during convulsive seizures. After MPTP treatment, a decrease in the 76 Br-Bromospiperone striatal specific binding was observed, correlated with the establishment of a Parkinson-like syndrome.

Animals↗

PubMed1985

Visualization by positron emission tomography of the apparent regional heterogeneity of central type benzodiazepine receptors in the brain of living baboons.

The feasibility of visualizing the heterogeneity of benzodiazepine (BDZ) receptors in the brain of living baboons was investigated using Positron Emission Tomography. Ethyl 8-fluoro-5,6-dihydro-5-methyl 6-oxo-4H-imidazo (1,5-a) (1, 4) benzodiazepine-3-carboxylate (RO 15 1788) labelled by carbon 11 (11C-RO 15 1788) was I.V. injected for the "in vivo" labelling of the central type BDZ receptors. Displacement experiments were performed 20 minutes after the administration of the radioligand by two different cold drugs: RO 15 1788 which has an equal affinity for central type BDZ receptors, and propyl B-Carboline-3-carboxylate (B-CCP) which favours the sites located in the cerebellum. Different sensitivities to these two drugs displacement of 11C-RO 15 1788 binding "in vivo" were observed: on the one hand in the regional localization of the displacement, and on the other hand, in the amount of the radioactivity displaced. The apparent interregional heterogeneity of the displacement seen in the cerebellum and in the temporal cortex are discussed in terms of discrepancies observed "in vitro" at physiological temperature, between cerebellar and non-cerebellar BDZ central type binding sites.

Animals↗

PubMed1985

Kinetics and displacement of [11C]RO 15-1788, a benzodiazepine antagonist, studied in human brain in vivo by positron tomography.

The brain regional distribution and kinetics of RO 15-1788, a benzodiazepine (BZD) antagonist labeled with 11C was studied by time-of-flight positron tomography after intravenous injection in four normal human volunteers. In two control studies, there was a high uptake of [11C]RO 15-1788 in gray matter structures initially (brain/blood ratio approximately 3), and subsequent retention that was highest in cerebral cortex, a structure known to have a high density of BZD receptors in vitro. Variation in tissue kinetics of [11C]RO among different gray matter structures may, however, suggest regional differences in binding characteristics or environment of BZD receptors. In two displacement studies, unlabeled RO 15-1788 was injected ten minutes after the radioligand: there was an immediate and marked washout of [11C]brain radioactivity that reached 70% in the occipital cortex with a 0.05 mg/kg dose (indicating a high specific to non-specific binding ratio) but was less prominent with a 0.01 mg/kg dose. These data suggest that [11C]RO 15-1788 may be useful for in vivo mapping of human brain BZD receptors using positron tomography.

Adult↗

PubMed1984

76Br-bromospiroperidol: a new tool for quantitative in-vivo imaging of neuroleptic receptors.

Bromine-76 labeled bromospiperone has been prepared with a very high specific activity (greater than 1 Ci/mumole). In-vivo studies in rat corroborated by PET studies in baboon have shown that the regional concentration of this radioligand parallels the morphologic distribution of dopamine receptors and that its binding in the striatum is saturable and displaceable. Tomographic images show a clear delineation of the striatal region 2.5 hours after administration of the radioligand.

Animals↗

PubMed1984

Central type benzodiazepine binding sites: a positron emission tomography study in the baboon's brain.

An in vivo characterization of specific central type benzodiazepine (BZD) binding sites, labelled with [11C]Ro 15-1788 was performed, using positron emission tomography. After i.v. injection of 10 mCi [11C]Ro 15-1788 (corresponding to 1 nmol/kg), sequential quantitative tomographic slices of the brain were obtained during 80 min. In some experiments various doses of different cold drugs (BZD agonist or antagonist) were injected i.v. subsequently in order to explore the specificity of the binding of the radioligand in brain structures. The main criteria usually utilized in vitro to demonstrate a specific binding to receptors, such as regional distribution, stereospecificity and saturability of the binding and pharmacological effect linked to the receptor's occupancy, were demonstrated in the brain of a living baboon.

Animals↗

PubMed1984

Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine-3-carboxylate (RO 15.1788-11C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography.

A method of labelling ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate (RO 15.1788 11C), a benzodiazepine antagonist with carbon-11 has been developed. RO 15.1788-11C was prepared by methylation of the nor derivative by I11CH3. About 100 mCi (maximum 153 mCi, 5.66 GBq) of the chemically and radiochemically pure labelled product were obtained within 25 min with a specific activity on average of 1100 mCi/mumol (maximum 1740 mCi/mu mol--64.4 GBq/mu mol). Preliminary results obtained after i.v. administration in the baboon have shown RO 15.1788-11C to be of interest as a benzodiazepine radioligand for the in vivo study of benzodiazepine receptors by positron emission tomography.

Animals↗

PubMed1983

[11C-Ro15-1788 and 11C-flunitrazepam, two coordinates for the study by positron emission tomography of benzodiazepine binding sites].

In vivo binding of a benzodiazepine (flunitrazepam-C11) and a benzodiazepine antagonist (Ro 15-1788-C11) were studied with positron emission tomography. Advantages and disadvantages of each drug for studying specific in vivo binding sites are presented. The results obtained indicate that Ro 15-1788-C11 is a better in vivo radiocoordinat than flunitrazepam-C11.

Animals↗

PubMed1983

[In vivo study of benzodiazepine receptors using positron emission tomography].

The results obtained by positron-emission tomography in an "in vivo" study on the baboon using a benzodiazepine (flunitrazepam) labeled with carbon-11 are presented. The specificity of "in vivo" binding of Flunitrazepam-11C was demonstrated by competition with Lorazepam in the brain, but it was not possible to verify the criterium of stereospecificity "in vivo". The preliminary results of a study carried out under the same conditions on RO 15 1788 11C show the interest of using this labeled antagonist as an "in vivo" ligand for the specific binding sites of benzodiazepines in positron-emission tomography.

Animals↗

PubMedDate not supplied

Relationships between benzodiazepine receptors, impairment of GABAergic transmission and convulsant activity of beta-CCM: a PET study in the baboon Papio papio.

Central type benzodiazepine receptors were studied in vivo by positron emission tomography in brain areas of 2 different groups of the baboon Papio papio: non-photosensitive (group 1) and those with an allylglycine-induced decrease in GABA-mediated inhibition (group 2). Further, a naturally photosensitive Papio papio (+3 level of photosensitive response) was compared to both groups. Regional brain binding of the specific benzodiazepine receptor ligand, [11C]Ro 15-1788, was not significantly different between groups 1 and 2. In addition, the data from the naturally photosensitive Papio papio did not seem to differ markedly from groups 1 and 2 either. Pharmacological effects of increasing doses of beta-CCM (0.05-3 mg/kg i.v.) and regional benzodiazepine receptor occupancy by the drug were simultaneously studied using electroencephalographic activity recording and positron emission tomography. A positive correlation was observed between the degree of photosensitivity of the baboon and sensitivity to the action of beta-CCM, with increasing convulsant efficacy of beta-CCM in going from group 1 to the naturally photosensitive baboon, then to group 2. Dose-related displacement curves of [11C]Ro 15-1788 binding by beta-CCM revealed that reduction in brain GABA concentration did not modify the inhibitory potency of beta-CCM on [11C]Ro 15-1788 binding in cerebral cortex. This suggests a lack of detectable in vivo allosteric effects of GABA on beta-CCM binding during beta-CCM-induced seizures. Thus, a given dose of beta-CCM displayed increasing pharmacological potency in going from baboons with the lowest photosensitivity to those with the highest, whereas benzodiazepine receptor occupancy by beta-CCM was similar in the cerebral cortex of the different baboons. Conversely, a given level of convulsant activity of beta-CCM was related to a different benzodiazepine receptor occupancy by the drug, depending on the photosensitivity of Papio papio. A given dose of a drug may, thus, have a different pharmacological potency when occupying the same number of receptors, depending on the physiopathological state of the subject.

Animals↗