Biomedical subjects

C Lemaire

Publications and source records attributed to C Lemaire.

At least 19 recordsLinked to original sources

PubMed1992

2- and 4-[18F]fluorotropapride, two specific D2 receptor ligands for positron emission tomography: N.C.A. syntheses and animal studies.

Tropapride, (exo)-2,3-dimethoxy-N-[8-(phenylmethyl)-8- azabicyclo[3.2.1]oct-3-yl]benzamide hydrochloride, has been labeled with fluorine-18 at the 2- and 4-positions of its benzylic group. Two synthetic pathways were investigated: the first one required the alkylation of the norbenzyl precursor with 2- or 4-[18F]fluorobenzyl bromide (radiochemical yield of 5% EOB, 180 min); the second method consisted of a reductive amination of norbenzyl tropapride with 2- or 4-[18F]fluorobenzaldehyde (20% EOB, 110 min). In both cases, the specific activity was found to be greater than 1 Ci/mumol (EOS). Animal studies in rats showed the percentage of the injected dose localizing in the whole brain to be 0.6 +/- 0.09 and 0.2 +/- 0.03 at 2 h post injection for the para- and the ortho-[18F]fluoro analogs of tropapride respectively. Cerebral biodistribution studies showed at 4 h a striatum uptake of 5 +/- 0.7% of the injected dose per gram of striatum for the para derivative with a low fixation into the frontal cortex and the cerebellum (% ID/g FC < 0.4 and % ID/g Cb < 0.3). The selectivity of 4-[18F]fluorotropapride for D2 dopaminergic sites was demonstrated through blocking experiments with ketanserin, spiperone and halopemide. The saturability was confirmed by the use of variable specific activities. These preliminary results showed that 4-[18F]fluorotropapride can be considered as a potent radiopharmaceutical for the study of the dopaminergic system with PET.

Animals↗

PubMed1992

Amino acids for the measurement of protein synthesis in vivo by PET.

In principle, PET in combination with amino acids labelled with positron-emitting radionuclides and kinetic metabolic models, can quantify local protein synthesis rates in tissue in vivo. These PET measurements have clinical potential in, for example, oncology, neurology and psychiatry. An optimal positron-emitting amino acid for the measurement of PSR has a high protein incorporation, can easily be prepared by automated equipment and has minimal non-protein radioactive metabolites. Presently L-[methyl-11C]methionine, L-[1-11C]leucine, L-[1-11C]tyrosine, L-[1-11C]phenylalanine, L-[1-11C]methionine and L-[2-18F]fluorotyrosine are under evaluation in normal volunteers and/or in patients. Several other amino acids are suggested. No comparison of the clinical usefulness of the different amino acids in man is yet available. Because of the longer half life of 18F compared to 11C, [18F]fluoro amino acids may have advantages over [11C]amino acids for the investigation of tissue with relative slow protein synthesis, such as brain, and for application in institutions with an off site, but nearby cyclotron. The half life of [13N]amino acids is considered to be too short for flexible clinical application. As yet no metabolic compartmental model has been investigated for [13N]amino acids. For routine application reliable preparation of the radiopharmaceutical is essential. Of all the amino acids under evaluation, a reliable, high yield, easy to automate production procedure is available for L-[methyl-11C]methionine only. It is however unlikely that this tracer can accurately measure PSR because of its non-protein metabolism. For the other amino acids the main problems in production are associated with complex multistep syntheses and/or low radiochemical yields, complex purification methods and the need to isolate the L-enantiomer. The kinetic metabolic models under investigation, consist of 4 or 5 compartments depending on the necessity to compensate for labelled metabolites. The metabolic profile of the amino acids is mainly extracted from animal experiments. Because of the number and amount of labelled metabolites in plasma, [11C]carboxylic labelled amino acids are preferred to amino acids with carbon-11 in another position. As yet no recommendation can be given on the optimal labelled amino acid(s) for PSR measurement in vivo nor on the methods to prepare the amino acids reported for this purpose.

Amino Acids↗

PubMed1992

Ligands and tracers for PET studies of the 5-HT system--current status.

The status of the radiochemical development and biological evaluation of radioligands and tracers for PET studies of the serotonergic system is reviewed, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies of central 5-HT2 receptors, namely [18F]setoperone and [18F]altanserin. Though, it has not proved possible to recommend tracers or radioligands for the study of other aspects of serotonergic system, prospects for future radiochemical development are indicated, especially for developing radioligands for the 5-HT re-uptake site, and for the 5-HT1 and 5-HT3 receptors.

Animals↗

PubMed1992

Concentration dependence of fluorine impurity spin-lattice relaxation rate in bone mineral.

The concentration dependence of the fluoride ion spin-lattice relaxation rate has been observed by nuclear magnetic resonance experiments on samples of defatted and dried bone. The 19F spin-lattice relaxation rates increased linearly with the bone fluoride concentration. Different results were obtained from trabecular than from cortical bone. For the same macroscopic fluoride content per gram of bone calcium, the relaxation rate is significantly faster in cortical bone. Relaxation rates in cortical bone samples prepared from both rats and dogs were apparently controlled by the same species-independent processes. For samples from beagle dogs, the bulk fluoride concentrations measured by neutron activation analysis were 3.1 +/- 0.3 times greater in trabecular bone than in the corresponding cortical bone. The beagle spin-lattice relaxation data suggest that the microscopic fluoride concentrations in bone mineral were 1.8 +/- 0.4 times greater in trabecular bone than in cortical bone. It is concluded that the accumulation of fluoride impurities in bone mineral is non-uniform.

Animals↗

PubMed1992

Evaluation of the integrity of the blood-brain barrier after meningeal trauma.

RATIONALE AND OBJECTIVES: The authors used magnetic resonance imaging (MRI) techniques to examine the effect of meningeal trauma produced by cisterna magna puncture on the integrity of the blood-cerebrospinal fluid barrier (BCB) in a rat model. METHODS: Intravenous gadolinium-DTPA (Gd-DTPA), a relaxation rate modifier which normally does not cross the BCB, was used as a probe to follow leakage of fluid across the BCB. After Gd-DTPA injection, cerebrospinal fluid (CSF) serial samples were obtained through the needle used to create the experimental trauma. These samples were subsequently examined in vitro by MRI to obtain their T1 relaxation rates and assayed by mass spectrometry for gadolinium and elemental iron concentrations. RESULTS: The iron levels reflected the severity of puncture-related subarachnoid hemorrhage. Rats with ongoing meningeal damage showed significantly higher CSF levels of gadolinium and significantly higher CSF T1 relaxation rates than controls at all samples times over 1 hour after the puncture. Blood in the CSF could not explain these changes because the CSF iron levels did not significantly differ from control levels. CONCLUSIONS: Intravenously administered Gd-DTPA can gain access to the subarachnoid space through minor defects in the BCB and cause significant increases in CSF T1 relaxation rates.

Animals↗

PubMed1992

High-resolution magnetic resonance imaging of experimental spinal cord injury in the rat.

The ability of magnetic resonance imaging (MRI) to display the anatomic changes after spinal cord injury in the rat were examined in postmortem specimens. With the clip compression technique, acute spinal cord injuries of three grades of severity were produced in adult male rats. One hour after injury, during which time physiological parameters were measured and maintained within the normal range, the rats were killed by transcardiac perfusion of formalin. The vertebral column containing the cervical and upper thoracic segments was excised and, after further formalin fixation, 20 contiguous MRI scans centered on the injury site were obtained using a spin-echo imaging sequence. The volume of signal acquisition for each image was 15 x 15 x 1.0 mm thick. The spinal cords were then removed from the vertebral column, sectioned, and stained for histological examination. Ten-micrometer serial sections of each cord were examined microscopically. MRI scans and microscopic sections at comparable levels were examined to determine the quality of anatomical detail and spatial resolution of the MRI scans. MRI scans with resolution of about 75 microns per pixel edge were obtained. At the site of injury, there was disruption of the normally well demarcated gray-white interface and variable areas of low signal intensity. Because of the resolution achieved, it was possible to determine that these low signal intensity areas were post-traumatic hemorrhages. Indeed, hemorrhages with dimensions of the order of 100 microns were detected on the MRI scans. Furthermore, by examining the serial sections of the cord, the extent of the injury along the cord could be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats.

No-carrier-added [18F]altanserin was synthesized by nucleophilic substitution of the corresponding nitro compound with [18F]fluoride in the presence of kryptofix 222 and K2CO3. After purification by preparative HPLC, [18F]altanserin was produced in less than 2 hr with a radiochemical yield of 10% (EOS) and a specific activity of 0.8-1.3 Ci/mumol. In rats, the tracer localized rapidly in the whole brain (0.5% ID/g organ) with a high binding to the frontal cortex. The frontal cortex/cerebellum ratio increased with time and reached a plateau of 11 at 2 hr postinjection. This uptake in S2 receptor regions was saturable and could be blocked by pretreatment with various S2 antagonists. This radiopharmaceutical appears to be more selective for S2 receptor sites than other ligands available today and allows the study of S2 receptors under in vivo conditions.

Animals↗

PubMed1991

Decrease of frontal metabolism demonstrated by positron emission tomography in a population of healthy elderly volunteers.

Frontal metabolism measured with positron emission tomography is shown to be decreased relatively to that in other cortical or sub-cortical areas, in a population of healthy elderly compared to young volunteers. Cortical atrophy or neuronal depopulation are unlikely to entirely explain this physiological phenomenon, and sub-cortico-cortical deactivation should play a role, analogous to that proposed in subcortical diseases.

Aged↗

PubMed1990

In vitro magnetic resonance microimaging of the spinal cord.

A 2.0-T small animal imager equipped with 3 G/cm imaging gradient coils was used to obtain images of en bloc segments of the vertebral column containing the rat spinal cord and of a cadaveric human spinal cord. These images demonstrate the applicability of MR micro-imaging techniques to the study of interesting problems in medicine and biology. Images of transverse sections of the spinal cord with in-plane resolution of better than 0.1 mm were obtained from slices 1 mm thick. The images of normal and injured rat spinal cord vividly show that spinal cord injury in the rat can be visualized using MRI techniques. The MR image of the cadaveric human spinal cord shows subanachroid gray and white matter structures. A comparison with a photomicrograph indicates that it is the superior contrast of the MR image that leads to increased conspicuity.

Animals↗

PubMed1990

Determination of extracellular/intracellular fluid ratios from magnetic resonance images: accuracy, feasibility, and implementation.

This study determines the accuracy and feasibility of using localized spin-lattice (T1) relaxation time measurements from magnetic resonance (MR) images to follow changes in extracellular/intracellular fluid ratios in defined subvolumes of living tissue. A red blood cell suspension was used as a test system and a simple two-compartment model incorporating fast exchange was found to suffice for the conversion of T1 values to volume ratios. The technique requires the addition of gadolinium-DTPA to the model system to selectively enhance relaxation in the extracellular fluid space. No detectable amount of gadolinium-DTPA was found to enter the intracellular fluid space, and all magnetization decay plots obtained from both intracellular constituents and complete RBC suspensions consisted of a single exponential. Both of these results are compatible with assumptions underlying our physical model. The NMR-determined fluid ratio values were compared to those measured via the microhematocrit technique. Partial saturation image-mode determinations are strongly correlated to microhematocrit data (R2 = 0.945) and indicate that localized cell volume changes may be followed with a sensitivity of +/- 2.2%. These values compare favorably with those produced when nonimaging inversion-recovery techniques are used to determine the MR hematocrit (R2 = 0.962, sensitivity = +/- 1.1%). This technique, with modification, should be applicable to the comparison of ratios of extracellular/intracellular fluid volumes in structurally complex tissues where small subvolumes of homogeneous cell structure could be examined.

Body Fluids↗

PubMed1990

Chemical processing for production of no-carrier-added selenium-73 from germanium and arsenic targets and synthesis of L-2-amino-4-([73Se]methylseleno) butyric acid (L-[73Se]selenomethionine).

The Ge(4He, xn) and 75As(p, 3n) reactions were compared as the best potential routes for routine production of selenium-73 (73Se) for medical applications. With 26 MeV alpha particles, available with compact cyclotrons, the first reaction required an enriched 70Ge target of sodium metagermanate to give a production yield of 1 mCi/microAh (0.037 GBq/microAh) in a 105 mg/cm2 target. With 55 MeV protons the As(p, 3n) reaction on natural arsenic yielded 20 mCi/microAh (0.74 GBq/microAh) in a 685 mg/cm2 target. A simple method was developed and optimized for both targets in order to isolate and purify the no-carrier-added selenium in the elemental form with a radiochemical yield greater than 75% in less than 90 min. An automated radiochemical processing unit has been designed for the routine production of 100-150 mCi (3.7-5.5 GBq) batches of carrier-free 73Se ready for radiopharmaceutical labeling. 30 mCi (1.11 GBq) (EOS) of L-2-amino-4-([73Se]methylseleno) butyric acid (L-[73Se]selenomethionine) ready for injection with a specific activity of 5 Ci/mmol (185 GBq/mmol) (EOS) were obtained through a fast chemical synthesis. Radiation absorbed dose estimates for L-[73Se]selenomethionine have been determined. A value of 0.70 rem/mCi (0.19 mSv/MBq) administered was calculated for the risk from irradiation in man. The first human PET investigation with [73Se]selenomethionine showed a very good delineation between liver and pancreas.

Arsenic↗

PubMed1990

Synthesis and tissue distribution of four Se-labeled tertiary amines, potential brain pH imaging agents.

Four new tertiary amines: bis(3-N,N-dimethyl aminopropyl)selenide (PROMOSE), bis(3-N-(morpholino)propyl)selenide, N-methyl-selenomorpholine and N-phenyl-selenomorpholine structurally related to MOSE proposed by Kung and Blau, have been labeled through a radiochemical procedure suitable for both 75Se and 73Se. The radiochemical yields of the carrier added synthesis ranged between 64 and 85% for the four 75Se labelings and was 64% EOB time corrected for [73Se]PROMOSE. The chemical and radiochemical purities were higher than 99% after chromatographic purifications. The n-octanol/phosphate buffer partition coefficients (P) were measured at various pH (6.5-8) for each compound and the tissue distributions of PROMOSE in rats were also carried out. The experimental results showed a good correlation between the P = f(pH) function and the in vivo behaviour of the considered compound. PROMOSE was selected for further investigations as a brain pH indicator.

Amines↗

PubMed1990

Field dependence of 19F NMR in rat bone powders.

The 19F NMR properties of fluoridated rat bone powder samples have been studied in several external magnetic fields. The results show a characteristic field dependence, related to the strength of chemical shift interactions compared to dipole-dipole interactions. While the free induction decay shape is relatively insensitive to the 19F bone mineral concentration, the spin-lattice relaxation time decreases with increasing 19F concentration. Multi-exponential spin-lattice relaxation processes indicate that there are at least two chemically inequivalent incorporation sites for fluorine in bone mineral. Evidence for clustering of 19F fluoride impurities in bone mineral is seen in Hahn echo experiments. Sample preparation and handling methods are shown to affect the values of some of the observed NMR parameters.

Animals↗

PubMed1990

No-carrier-added regioselective preparation of 6-[18F]fluoro-L-dopa.

This paper describes the preparation of 6-[18F]fluoro-L-dopa by a no-carrier-added method based on the nucleophilic displacement of nitro groups of two commercially available substrates, 3,4-dimethoxy-2-nitrobenzaldehyde (nitroveratraldehyde) and 6-nitropiperonal. Fluorination was conducted in DMSO with fluorine-18 (18F) in the presence of the aminopolyether Kryptofix 222 and potassium carbonate. The condensation of the fluorinated aldehydes with phenyloxazolone and the subsequent hydrolysis with HI/P yield, after purification by HPLC, only the 6-(D, L) isomers. The racemic mixture (50/50) was resolved on an analytical scale chiral column. The method, which requires 100 min (EOB) to complete, produces 6-[18F]fluoro-L-dopa with a decay-corrected radiochemical yield of 10%, an enantiomeric purity greater than 99%, and a specific activity of 1.2 Ci/mumole.

Benzaldehydes↗

PubMed1989

The chloroplast ATP synthase in Chlamydomonas reinhardtii. I. Characterization of its nine constitutive subunits.

We have characterized the subunit composition of the chloroplast ATP synthase from Chlamydomonas reinhardtii by means of a comparison of the polypeptide deficiencies in a mutant defective in photophosphorylation, with the polypeptide content in purified coupling factor (CF)1 and CF1.CF0 complexes. We could distinguish nine subunits in the enzyme, four of which were CF0 subunits. Further characterization of these subunits was undertaken by immunoblotting experiments, [14C]dicyclohexylcarbodiimide binding and analysis of their site of translation. In particular, we were able to show the presence of an as yet unidentified delta subunit in CF1 from C. reinhardtii. We have identified a 70-kDa peripheral membrane protein in the thylakoid membranes of C. reinhardtii, which is immunologically related to the beta subunit of CF1. We discuss its conceivable ATPase function with respect to the Ca2+-dependent ATPase activity previously reported in the thylakoid membranes from C. reinhardtii.

Chlamydomonas↗

PubMed1989

The chloroplast ATP synthase in Chlamydomonas reinhardtii. II. Biochemical studies on its biogenesis using mutants defective in photophosphorylation.

We have carried out an analysis of the synthesis, cellular accumulation, and membrane binding of the chloroplast-encoded subunits of the ATP synthase (alpha, beta, epsilon, I, III, and IV) in several mutants of Chlamydomonas reinhardtii defective in photophosphorylation. These data gave some insight on the putative genetic lesion in each mutant and allowed some characterization of the assembly and stabilization of the ATP synthase complex in the thylakoid membranes. Four chloroplast mutants are likely to be altered in chloroplast structural genes coding for coupling factor (CF) 1 subunits beta and epsilon and for CF0 subunits I and IV. A fifth chloroplast mutant and three nuclear mutants were altered in genes regulating either transcription or translation of chloroplast genes coding for CF1 subunits alpha and beta and CF0 subunits III and IV. Evidence is presented (i) for a control of the rate of synthesis of subunit beta by subunit alpha in the absence of ATP synthase assembly and (ii) for an interaction between alpha and beta subunits in the stroma of the chloroplast which protects alpha subunits from proteolytic degradation. The role of several chloroplast-encoded subunits of CF0 and CF1 in the stabilization of partially assembled ATP synthase is discussed. We conclude that in the absence of ATP synthase assembly, CF0 cannot accumulate in the thylakoid membranes, whereas alpha and beta subunits, presumably engaged in soluble CF1, can accumulate in the stroma of the chloroplast.

Chlamydomonas↗

PubMed1989

Magnetic resonance imaging of silastic-induced canine hydrocephalus.

Nine adult beagle dogs underwent magnetic resonance imaging in a 2-Tesla small-bore unit. Six surviving dogs were followed up serially with magnetic resonance imaging after induction of hydrocephalus by injection of Silastic into the prepontine cistern or fourth ventricle. Ventricular size (Y) measured as percentage cross-sectional area of an anterior frontal slice was related to postoperative day (X) as Y = 1.54 + 4.21 x ln(X), r = 0.9596. Periventricular edema appeared initially in the superlateral angles of the frontal horns in an area that corresponded histologically to the subcallosal fasciculus. T1 relaxation time of normal white matter of 979.32 msec increased to 1813.90 msec in the area of the edema (p less than 0.0001). The T2 relaxation time of normal white matter of 83.39 msec increased to 238.26 msec in the area of the edema (p less than 0.0001). Histological changes included expansion of the extracellular space in an area comparable to the region of increased signal intensity on T2-weighted images, as well as diffuse astrocytosis in the chronically hydrocephalic dogs.

Animals↗

PubMed1989

Cerebrospinal fluid shunts: flow measurements with MR imaging.

The authors describe a technique for determination of shunt patency by quantifying cerebrospinal fluid shunt flow rates with magnetic resonance (MR) imaging. This method uses a modified clinical sequence that is both sensitive to slow flow perpendicular to the imaging plane and capable of achieving oblique angles with a 4-cm field of view. Velocity-dependent phase images were used to quantify flow rates within the shunt. A preliminary study was performed in seven patients with hydrocephalus and cerebrospinal fluid shunts. Two patients were found to have zero flow in the shunt, while the remaining five had flow rates ranging from 4 to 19 mL/h. Results showed that the measurement of flow rates within the shunt lumen with MR imaging is clinically feasible.

Adolescent↗