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Biomedical subjects

C Loc'h

Publications and source records attributed to C Loc'h.

At least 55 records · Page 3Linked to original sources
PubMed1993

Bromine-76-metabromobenzylguanidine: a PET radiotracer for mapping sympathetic nerves of the heart.

Iodine-123-metaiodobenzylguanidine (MIBG) is used to qualitatively assess heart innervation with single-photon emission computed tomography (SPECT). This approach is clinically useful in the prognostic evaluation of congestive heart failure. To improve quantification of uptake of the tracer using positron emission tomography (PET), we studied the characteristics of the bromoanalog of MIBG. Bromine-76-metabromobenzylguanidine (76Br-MBBG) was prepared from a heteroisotopic exchange between radioactive bromine atoms (noncarrier-added (76Br) BrNH4) and the cold iodine atoms of the precursor metaiodobenzylguanidine. Biodistribution was studied in rats and PET cardiac imaging performed in dogs. Myocardial uptake was high and prolonged in both species (mean half-life in dogs: 580 min). In rats, myocardial uptake was inhibited by desipramine by 64%, whereas after pretreatment with 6-hydroxydopamine uptake was reduced by 84%. In dogs pretreated with 6-hydroxydopamine or with desipramine, a steep washout of the tracer occurred (mean half-life: 136 min and 118 min, respectively). The non-specific uptake plus the passive neuronal diffusion of the tracer could be estimated at about 25%-30% of the total fixation. In dogs, analysis of unchanged 76Br-MBBG in plasma showed that radiotracer metabolism was slow: 60 min after injection, 80% of the radioactivity was related to unchanged 76Br-MBBG. These preliminary findings suggest that 76Br-MBBG could be used to quantitatively assess adrenergic innervation in heart disease using PET. When combined with use of 11C-CGP 12177, cardiac adrenergic neurotransmission can be assessed.

3-Iodobenzylguanidine↗
PubMed1992

In-vivo SPECT imaging of D2 receptor with iodine-iodolisuride: results in supranuclear palsy.

We assessed the potential use of [123I]iodolisuride (ILIS), a new iodine ergolene derivative, to study human striatal D2 dopamine receptors with SPECT. In normal subjects, we found that the tracer accumulated preferentially in striatum. This was prevented by high doses of haloperidol. The striatal accumulation was maximal between 60 and 180 min after injection. The striatum-to-cerebellum radioactivity concentration ratio as an index of specific binding, measured 60 min after injection, was 1.52 +/- 0.19 (mean +/- s.d.) in controls and 1.36 +/- 0.11 in patients with supranuclear palsy (p less than 0.03). Our results show that ILIS may be used to study D2 receptors with SPECT. In-vivo changes of D2 receptors in human brain may be detected with this method.

Adult↗
PubMed1991

The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study.

We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose [18FDG]). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.

Animals↗
PubMed1991

Kinetic analysis of central [76Br]bromolisuride binding to dopamine D2 receptors studied by PET.

The in vivo kinetic analysis of dopamine D2 receptors was obtained in baboon brain using positron emission tomography (PET) and [76Br]bromolisuride [( 76Br]BLIS) as radioligand. An injection of a trace amount of [76Br]BLIS was followed 3 h later by an injection of a mixture of [76Br]BLIS and BLIS in the same syringe (coinjection experiment). A third injection performed at 6 h was either an excess of unlabeled ligand (displacement experiment) or a second coinjection. This protocol allowed us to evaluate in the striatum of each animal and after a single experiment the quantity of available receptors (B'max) and the kinetic parameters including the association and dissociation rate constants (k + 1VR and k-1, respectively, where VR is the volume of reaction). The cerebellum data were fitted using a model without specific binding. All the parameters were estimated using nonlinear mathematical models of the ligand-receptor interactions including or not including nonspecific binding. The plasma time-concentration curve was used as an input function after correction for the metabolites. An estimate of standard errors was obtained for each PET study and for each identified parameter using the covariance matrix. The average values of B'max and KdVR were 73 +/- 11 pmol/ml tissue and 1.9 +/- 0.9 pmol/ml, respectively. The nonspecific binding was identifiable in the experiment where the last injection corresponded to a second coinjection. We found that approximately 6% of the striatal binding was nonspecific after a tracer injection of [76Br]BLIS. The nonspecific binding appeared to be reversible in the striatum but irreversible in the cerebellum.

Animals↗
PubMed1991

The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride.

The striatal D2 receptors of 19 untreated schizophrenics and 14 normal control subjects were investigated with PET and 76Br-bromolisuride. The ratio of radioactivity in the striatum to that in the cerebellum was taken as an index of the striatal D2 receptor density. There was no significant difference between the control and the schizophrenic groups, nor any difference between subgroups of patients defined by clinical type or course of illness, and no relationship between the striatum:cerebellum activity ratio and SANS or SAPS ratings of symptoms. Unlike in the controls, this ratio was not correlated with age in schizophrenics. This study suggests that there is no quantitative abnormality of striatal D2 dopamine receptors in schizophrenia.

Adolescent↗
PubMed1991

Cardiac beta-adrenergic receptor density measured in vivo using PET, CGP 12177, and a new graphical method.

The in vivo quantification of myocardial beta-adrenergic receptor has been obtained in five closed-chest dogs using positron emission tomography (PET). The ligand was racemic (+/-)[11C] CGP 12177, a very potent hydrophilic antagonist of the beta-adrenergic receptor. A kinetic method appeared unsuitable because of the presence of metabolites which made the input function difficult to measure and also inaccurate. Therefore, a graphical method, based on a particular protocol, was proposed. The animals were injected with a trace amount of (+/-)[11C]CGP 12177, which was followed 40 min later by a second injection of radioligand with a low-specific activity. An additional injection of an excess of unlabeled CGP 12177 was administered after 90 min and allowed for the estimation of the dissociation rate constant. The main advantage of this graphical approach is that the results are obtained without having to measure the input function and therefore without estimating the metabolites. The average value of Bmax was 31 +/- 4 pmole/ml of tissue and the dissociation constant was 0.014 +/- 0.002 min-1.

Adrenergic beta-Antagonists↗
PubMed1990

Striatal D2 dopaminergic receptors assessed with positron emission tomography and [76Br]bromospiperone in untreated schizophrenic patients.

Striatal D2 dopaminergic receptors of 12 drug-free schizophrenic patients and 12 normal subjects were investigated with positron emission tomography and [76Br]bromospiperone. Patients were classified according to DSM-III criteria, and their clinical symptoms were rated according to Andreasen's negative and positive symptom scales. The ratio of striatal to cerebellar radioactivity was taken as an index of striatal D2 dopamine receptor density. There was no significant difference between the control subjects and the overall schizophrenic group and no significant relationship between this index and the symptom ratings. However, state-dependent variables could partly account for the striatal D2 receptor density variability.

Adult↗
PubMed1989

Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels.

The percentage occupation of striatal dopamine D2 receptors has been evaluated in 25 patients using 76Br-bromospiperone positron emission tomography (PET) and prolactin plasma levels (PRL) during oral neuroleptic treatment (11 studies), 1-90 days following discontinuation of such treatment (16 studies), and 1-120 days after last intramuscular administration of depot neuroleptics (nine studies). The PET-estimated occupation was highly significantly correlated in a sigmoid-like fashion to the logarithm of the chlorpromazine-equivalent dose of oral neuroleptics (suggesting a strict dose-occupation relationship during oral neuroleptic treatment and supporting the D2-mediated hypothesis of neuroleptic action), while PRL was weakly related to daily dosage. Following withdrawal, return to normal receptor availability, as estimated by PET, occurred within 5-15 days (suggesting that protracted effects of neuroleptics after withdrawal are not due to sustained D2 receptor occupation), but PRL values fell even more rapidly. Efficient treatment with depot neuroleptics resulted in marked PET-estimated D2 receptor occupation, stable over the whole 4-week drug-administration interval, suggesting that longer intervals could be appropriate; PRL values bore no relationship to PET-estimated occupation, indicating variable intersubject tolerance to neuro-endocrine dopamine blockade. Overall, PET was much more sensitive than PRL to estimate striatal D2 receptor occupation in vivo.

Adult↗
PubMed1989

Striatal dopamine D2 receptors in tardive dyskinesia: PET study.

The dopamine D2 receptors were investigated in vivo in eight neuroleptic-free patients with persistent tardive dyskinesia using positron emission tomography and 76Br-bromospiperone. The striatal receptor density, estimated by the striatum/cerebellum radioligand concentration ratio, was not elevated in patients as compared with age-matched controls but was positively correlated with the severity of orofacial dyskinesia assessed with the Abnormal Involuntary Movement Rating Scale. These results indicate that tardive dyskinesia is associated with normal levels of striatal D2 receptors but the severity of orofacial movements may depend on the relative density of striatal D2 receptors.

Aged↗
PubMed1988

Regional cerebral opioid receptor studies with [11C]diprenorphine in normal volunteers.

The results are described of the cerebral uptake and heterogeneous retention of [11C]diprenorphine after intravenous injection in 4 normal volunteers. This potent opioid antagonist (Kd = 0.2 nM) was chosen because of its safety, lack of side-effects at trace doses in human pilot studies, rapid cerebral uptake and high percentage (80-90%) specific binding in animal in vivo studies. High uptake of [11C]diprenorphine was demonstrated in regions such as the thalamus, caudate nucleus, temporal, frontal and parietal cortices, which are known from postmortem studies to have high concentrations of opioid receptors. A stable level of activity or a very slow decline in activity was observed between 20 and 50 min after injection in areas such as the caudate nucleus and thalamus. Conversely, rapid washout of activity was observed in the occipital cortex, which is known to have low opioid receptor concentrations. Some 80-90% of maximum binding was naloxone reversible. These results with a ligand that is safe and without side-effects, suggest that this technique is suitable for studies of opioid physiology in man.

Brain↗
PubMed1988

Anatomical atlas of the baboon's brain in the orbito-meatal plane used in experimental positron emission tomography.

An anatomical atlas has been constructed of the brain of the baboon (Papio papio) in the orbito-meatal plane (OM-plane) which is frequently used in experimental positron emission tomography (PET) investigations. The atlas comprises 12 photographic reproductions of histological brain sections separated by 2.5 mm intervals, and covers telencephalic to pontine brain stem levels. The anatomical atlas was used in analysis of some PET scan images obtained after administration of either a benzodiazepine (BZ) antagonist, (11C)-Ro 15-1788, or a dopamine D2 receptor antagonist, (76Br)-bromospiperone. Since PET camera detects radiation emitted from a slice of tissue of 15 mm thickness, each PET image corresponds to the tissue represented on six levels of the anatomical atlas. In optimal conditions, the PET image shows a pattern of receptor labelling reminiscent of anatomical structures in the atlas. Sometimes, however, the superimposition of different labelled structures yields a PET image which lacks any apparent resemblance with individual anatomical structures. In these cases, the analysis of the PET scan must rely on the anatomical atlas, as well as available data on the distribution of specific binding sites.

Animals↗
PubMed1987

In vivo assay for neuroleptic receptor binding in the striatum. Positron tomography in humans.

Using PET, we investigated the potency in six patients of therapeutic doses of neuroleptic drugs for preventing specific binding of trace doses of intravenously administered 76Br-labelled bromospiperone to corpus striatum in vivo. Measured receptor occupancy showed a clear-cut dose-dependent saturation curve with increasing daily oral dose of neuroleptics, indicating the validity and reliability of the method when used as an in vivo radioreceptor assay. Following drug withdrawal in eight patients, recovery to normal or supranormal receptor availability occurred in a matter of days. The results demonstrate an approach that may help resolve controversies about, and design better strategies for, neuroleptic treatment schedules.

Adult↗
PubMed1986

"In vivo" visualization by positron emission tomography of the progressive striatal dopamine receptor damage occurring in MPTP-intoxicated non-human primates.

Intravenous administration of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) leads to the progressive development of a model of Parkinson's disease in the primate. The development of damage occurring in the striatal area during MPTP-treatment was followed "in vivo" in a baboon by positron emission tomography (PET). Spiperone labelled with a positron emitter 76Br (76Br-BSP) was used for the quantitative "in vivo" imaging of D2 dopamine receptors. The decrease in the striatal binding of 76Br-BSP measured "in vivo", after three series of MPTP injections, paralleled the increase in the severity of behavioral symptoms seen immediately after administration of the neurotoxin. At the end of the MPTP-treatment when neurological symptoms were the most important, a 36% decrease in the 76Br-BSP specific binding was measured. Between the series of MPTP injections a partial recovery in the quantitative measurement of the 76Br-BSP specific binding occurring in the striatum was well correlated with the disappearance of the neurological syndrome. Post-mortem histological and biochemical studies in nigro-striatal anatomical structures of MPTP-intoxicated primates compared with control animals showed a 80% loss of neuronal cell bodies in the substantia nigra compacta and a 42% decrease in the density (Bmax) of D2 receptors (in vitro 3H-spiperone binding). All these results showed that the use of PET and 76Br-BSP allow to follow in a noninvasive way both the degenerative processes and the subsequent partial recovery which occur in dopaminergic striatal receptor function during MPTP-treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
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

Stable labelling of serum albumin microspheres with gallium-68.

A highly efficient and rapid technique for labelling serum albumin microspheres with 68Ga is described. Measurements of the in vivo stability of the radiopharmaceutical in the rabbit and the baboon show that less than 0.2% of the injected activity is eluted from the microspheres in 2 h.

Animals↗