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Biomedical subjects

M Guillaume

Publications and source records attributed to M Guillaume.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effect of age on the disposition of sodium fluoride.

Sodium fluoride (NaF) is used in the treatment of axial osteoporosis and so is mostly given to old patients. Since its pharmacokinetics has not been studied in the elderly, the pharmacokinetics of an enteric-coated tablet containing 50 mg NaF has been investigated in 15 aged inpatients (aged 65 to 75 y) and 12 young healthy volunteers (aged 21 to 26 y). The serum AUC of fluoride was 1.7-time higher in older than in younger subjects. There was a strong inverse correlation between the AUC and either body surface area (BSA) or glomerular filtration rate (GFR), both of which were very much lower in the elderly. This concluded that if efficacy or safety are related to the bioavailability of fluoride, it may be valuable to adjust the dosage of fluoride accordingly to the GFR and BSA.

Adult↗
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

Production of 6-[18F]fluoro-L-dopa and its metabolism in vivo--a critical review.

This report critically appraises methods for the synthesis of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (6-FDOPA) that are based on labelling by non-regioselective electrophilic fluorination, regioselective fluorodemetalation or nucleophilic substitution. Recommendations for the standardization of labelling procedures, the optimization of radiochemical yield and the assurance of product quality and safety are given. Studies of the metabolism of 6-FDOPA in vivo are also reviewed to emphasize the importance of the biochemical component of the development of this tracer for positron emission tomography (PET).

Animals↗
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

Diagnosis of venous thrombosis in the legs using 81Krm venography.

Contrast venography, the accepted gold standard for the diagnosis of venous thrombosis of the leg, is a painful and invasive procedure with late side effects. There is controversy in literature reports about the sensitivity of 99Tcm-macroaggregated albumin (MAA) phlebography: indeed, using 99Tcm-MAA, poor results are obtained when one has to detect calf vein thrombosis. As with other isotopic procedures requiring a pedal injection of the tracer, the use of an injectable solution of 81Krm is a nonspecific method, based upon the abnormality in flow in the deep venous system which results from a deep venous thrombosis. However, when compared with 99Tcm-MAA, 81Krm offers theoretical advantages for phlebographic studies of the lower limbs. In this work 24 patients were studied both with contrast phlebography and with 81Krm. Although 81Krm provided images of high quality, there was a lack of sensitivity below the knee, where false negative results were observed. This could be explained by the fact that the radionuclide venographic procedures usually visualize only one or, in some cases, two of the three deep veins of the calf. Moreover, accurate differentiation between superficial and deep veins in the calf often appears difficult, even using a tourniquet.

Humans↗
PubMed1991

The synthesis of no-carrier-added DL-4-[18F]fluorodeprenyl via the nucleophilic aromatic substitution reaction.

No-carrier-added DL-alpha-methyl-beta-4-[18F]fluorophenyl-N-methyl-N-propynylethylamin e (DL-4-[18F]fluorodeprenyl) was synthesized via the following 3-step procedure: (1) nucleophilic aromatic substitution by [18F]fluoride on 4-nitrobenzaldehyde to produce 4-[18F]fluorobenzaldehyde (yield 65%); (2) the reaction of 4-[18F]fluorobenzaldehyde with (1-chloro-1-(trimethylsilyl)ethyl)lithium followed by hydrolysis to give 4-[18F]fluorophenylacetone (yield 50%); and (3) reductive alkylation of 4-[18F]fluorophenylacetone with N-methyl-propynylamine in the presence of NaBH3CN (yield 35%) followed by HPLC purification to give a racemic mixture of 4-[18F]fluorodeprenyl. The overall yield was 11% (EOB corrected), the synthesis time was 90 min and the specific activity greater than 0.57 Ci/mumol (end of synthesis). This synthesis approach, the conversion of an aromatic aldehyde to a homologous methyl ketone, extends the flexibility of the nucleophilic aromatic substitution reaction by applying it to the synthesis of radiotracers which do not bear electron-withdrawing activating groups on the aromatic ring. The tissue distribution of DL-4-[18F]fluorodeprenyl in mice at 1, 10 and 60 min was also measured and showed that metabolic defluorination was not significant. Clearance of radioactivity from brain after injection of DL-4-[18F]fluorodeprenyl was more rapid than that previously observed for [11C]L-deprenyl.

Animals↗
PubMed1991

Performance of a single crystal digital gamma camera for first pass cardiac studies.

First pass radionuclide angiocardiography (FPRNA) has gained increasing interest because of the development of new 99Tcm-labelled perfusion agents and of new 191Os/191Irm generator systems. The aim of the study was to evaluate the performance capacities of a small field of view single crystal digital gamma camera for 99Tcm and 191Irm at high count rates. The camera dead time for 99Tcm (window 30%) was well corrected up to 300 kcps in fast acquisition mode using the relative decrease of a small shielded reference source. Using the decaying activity method for 191Irm the non-linearity response of the gamma camera was corrected by an 191Os reference soruce up to 210 kcps at 70 keV, 75 kcps at 129 keV and 320 kcps including both peaks. Saturation count rates were respectively 270 kcps, 150 kcps and 420 kcps and high count rate resolution (FWHM) 9.0, 7.3 and 10.3 mm. Since the accuracy of first pass measurements is more sensitive to count rate than to spatial resolution the 50-150 keV window was chosen for clinical studies. In data obtained from 32 ECG gated FPRNA patient studies, the whole field of view count rate during the left ventricular phase ranged from 100 to 250 kcps with 80 to 120 mCi (2960-4400 MBq) of 191Irm and 100 to 180 kcps with 20 to 25 mCi (750-925 MBq) of 99Tcm red blood cells permitting for both tracers accurate non-linearity correction.

Evaluation Studies as Topic↗
PubMed1991

Comparison between exercise myocardial perfusion and wall motion using 201Tl and 191Irm simultaneously.

By exploiting the ultrashort half-life 191Irm as tracer for left ventricular first-pass angiocardiography and 201Tl as myocardial perfusion agent, direct comparison between myocardial perfusion and regional wall motion was obtained during the same exercise stress test in patients with non-significant coronary artery disease, in patients with recent myocardial infarction, and in patients six weeks after successful percutaneous transluminal coronary angioplasty (PTCA). A good agreement between regional myocardial perfusion and regional wall motion was observed in patients with non-significant coronary artery disease and in most patients with recent myocardial infarction. In contrast, discrepancies occurred at maximal exercise in patients studied six weeks after successful PTCA: only 38% of the patients with no evidence of restenosis and with a completely normal myocardial perfusion scintigraphy had a normal regional wall motion at maximal exercise stress. According to these results, a normal uptake of 201Tl six weeks after PTCA would mean that the circulation has been successfully reestablished but without predicting the functional capacities of the myocardial cells which remain altered at least six weeks after the revascularization procedure in about two-thirds of the patients. We conclude that 191Irm in combination with 201Tl offers the opportunity of performing myocardial perfusion and wall motion studies simultaneously both at rest and during exercise.

Adult↗
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↗
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

Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl and positron emission tomography studies in baboon brain.

(R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine [R)-(-)- and (S)-(+)-4-fluorodeprenyl) were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recrystallization with L- or D-N-acetylleucine to yield (R)-(-)-4-fluoroamphetamine or (S)-(+)-4-fluoroamphetamine in greater than 96% enantiomeric excesses and in yields of 42 and 39%, respectively. Alkylation with propargyl bromide gave (R)-(-)- or (S)-(+)-4-fluoronordeprenyl which was reductively methylated (Borch conditions) to produce (R)-(-)- or (S)-(+)-4-fluorodeprenyl. Alkylation of (R)-(-)- or (S)-(+)-4-fluoronordeprenyl with carbon-11 labeled methyl iodide gave (R)-(-)- or (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl in a radiochemical yield of 30-40%. Comparative PET studies of the two labeled enantiomers in baboons showed a significantly lower retention of radioactivity in the striatum for the (S)-(+) enantiomer relative to the (R)-(-) enantiomer.

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

Prediction of pulmonary arterial pressure in chronic obstructive pulmonary disease by radionuclide ventriculography.

Pulmonary arterial hypertension represents an important parameter for the assessment of the severity of chronic bronchitis. The measurement of the pulmonary arterial pressure, however, requires invasive techniques of limited routine use because of costs and associated risks. The aim of this study is to evaluate whether the 81mKr right ventricular ejection fraction and parameters derived from equilibrium 99mTc red blood cells' right ventricular curve allow a better estimation of PAP than the 99mTc RVEF. In 41 patients with severe chronic bronchitis, the linear correlation between PAP and 99mTc RVEF was -0.61 (p less than 0.001). None of the parameters derived from the right ventricular curve was better correlated to PAP than the 99mTc RVEF. In 16 other chronic bronchitis patients, the 81mKr RVEF correlated moderately to PAP. In conclusion, the alternative isotopic methods proposed in this work do not provide a reliable estimation of pulmonary arterial pressure in patients with chronic bronchitis.

Blood Pressure↗
PubMed1989

[Upper jejunal atresia: treatment using jejunal resection, duodenal modeling and duodeno-jejunal or ileal anastomosis. Results in 13 newborn infants].

13 high jejunal atresias, including 6 type IIIb apple peel small bowel deformities, have been treated by a one stage surgical procedure, including proximal jejunal resection, tapering duodenoplasty and end-to-end duodeno-jejunal or duodeno-ileal anastomosis. All 13 infants survived. There were no anastomotic leak or malfunction. 7 jejunal atresias with normal distal small bowel were fed a mean of 9 days post-operatively (range 4 to 12 days). Intra-venous fluids were discontinued at a mean of 18 days post-operatively (range 13 to 24 days). Patients, all premature babies, were discharged on the mean 30th post-operative day (range 24 to 40). 5 jejunal atresias with apple peel deformity were fed with an average post-operative delay of 21 days (range 12 to 24). All intra-venous fluids were discontinued at a mean of 48 days post-operatively (range 35 to 90). Average hospital stay was 78 days (45 to 120). In one case, an ileal diaphragm, unnoticed during the first operation was subsequently resected at age 45 days and an iterative tapering duodenoplasty was performed at the age of 8 months. Recovery was then uncomplicated and the child was discharged on a normal oral feeding at the age of 10 months. Functional obstruction of the intestine at the site of anastomosis often occurs in high jejunal atresias. 70% of mortality resulted from operative complications in atresias with apple peel deformity. Intestinal distension is the cause of anastomotic malfunction. After jejunal resection, the duodenum remains dilated and anastomosis cannot function properly.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1989

Clinical usefulness of ultrashort-lived iridium-191m from a carbon-based generator system for the evaluation of the left ventricular function.

Ultrashort-lived 191mIr (4.96 sec; 63-74 and 129 keV photons) is potentially advantageous for first-pass radionuclide angiocardiography, offering the opportunity to perform repeat studies with very low absorbed radiation dose to the patient. Left ventricular (LV) first-pass studies were performed in 72 patients with 191mIr from a new bedside 1.3 Ci (48.1 GBq) 191Os/191mIr generator system using an activated carbon support that offers high 191mIr yields (15-18%) and consistent low 191Os breakthrough (2-4 x 10(-4)%/bolus). Using a single crystal digital gamma camera, uncorrected end-diastolic counts in the left ventricular representative cycle ranged from 10 up to 30 k counts. The reproducibility of repeated LV ejection fraction (LVEF) determination at 2-min intervals in 50 patients was r = 0.97, mean diff. = 2.08 +/- 1.55 EF units. Comparison between 191mIr (80-120 mCi; 2,960-4,400 MBq) and 99mTc (20-25 mCi; 750-925 MBq) LV count rates indicates a 3 wk useful shelf life of this new generator system for cardiac studies. Iridium-191m determined LVEF correlated closely with 99mTc determined LVEF in 32 patients (r = 0.96, mean diff. = 1.87 +/- 1.23 EF units). Parametric images for LV wall motion analysis were comparable with both isotopes. We conclude that rapid, repeat, and reproducible high count rate first-pass left ventricular studies can be obtained with 191mIr from this new 191Os/191mIr generator system using a single crystal digital gamma camera.

Adult↗