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J C Besnard

Publications and source records attributed to J C Besnard.

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

Estrogen receptor imaging with 17 alpha-[123I]iodovinyl-11 beta-methoxyestradiol (MIVE2)--Part I. Radiotracer preparation and characterization.

It is important to know the estrogen receptor rate in breast carcinoma management. Thus, an in vivo and atraumatic method would be very useful. Different ligands have been proposed for this. We present here the specific synthesis of 20E- and 20Z-17 alpha-iodovinyl-11 beta-methoxyestradiols and their biological characterization as estrogen receptor ligands. The two isomers were analysed by current chemical methods (NMR) and purified by HPLC. We carried out an in vivo study with 21-day-old Swiss mice to compare properties of the two ligands. The 20E-MIVE2 showed the best affinity for estrogen receptors, the uterus-to-blood ratio was 15-fold higher for the trans derivative. We enhanced the in vivo and in vitro properties of the 20E-MIVE2: the affinity constant was determined by Scatchard analysis, Kd = 16 x 10(-10) M, and biodistributions were performed with unlabelled estradiol pre-injection. We concluded that 20E-MIVE2 can be used for a feasibility study in patients with breast carcinoma.

Animals↗
PubMed1992

Estrogen receptor imaging with 17 alpha-[123I]iodovinyl-11 beta-methoxyestradiol (MIVE2)--Part II. Preliminary results in patients with breast carcinoma.

17 alpha-[123I]Iodovinyl-11 beta-methoxyestradiol was injected into 19 women: group 1 (n = 8), initial evaluation of breast cancer; group 2, (n = 11) postoperative follow-up including 9 patients with bone metastases. The primary tumor (size: 8-10 mm) was visualized by breast tomoscintigraphy in 2/4 patients of group 1 with high estrogen receptor concentration (162-445 fmol/mg) and was not detectable in 4 patients with low estrogen receptor concentration (6-32 fmol/mg). Axillary lymph node metastases were detected in 1 patient of group 1 and in 1 patient of group 2. In 4 patients of group 2 with previous primary tumor containing estrogen receptors, MIVE2 uptake in bone metastases was demonstrated. MIVE2 scintigraphy is an original, specific and non-invasive method for breast cancer estrogen receptor imaging in primary and in metastatic tumors.

Adult↗
PubMed1992

Synthesis and in vitro binding properties of halogenated analogues of GBR as new dopamine uptake carrier ligands.

We present the original synthesis of two halogenated analogues of the diphenyl piperazine GBR, bromo-GBR and iodo-GBR, as new dopamine uptake carrier ligands. The derivatives were purified by HPLC and chemically characterized. Bromo-GBR and iodo-GBR and iodo-GBR are potent inhibitors of [3H]GBR 12935 binding to rat striatal membrane, with Ki values of 116 and 113 nM, respectively. We prepared iodo-GBR labeled with iodide-125 from the brominated derivative and concluded that [123I]iodo-GBR could be a potential tool to explore the in vivo dopamine uptake carrier.

Animals↗
PubMed1992

Multicentre evaluation of a two-step automated enzyme immunoassay of free thyroxine.

The two-step enzymatic immunoassay of free thyroxine (IMx FT4, Abbott Laboratories, Chicago, IL) was studied in three centres. The assay involved a fluorimetric measurement and took 45 minutes using a completely automated procedure. The results were compared with those from the free thyroxine two-step radioimmunoassay and with the "calculation" of free thyroxine. The analytical precision was found to be excellent if the analyser was correctly set. The IMx FT4 assay seemed unaffected by increased concentrations of albumin and of non-esterified fatty acids (oleic acid) up to 5 mmol/l. The euthyroid reference interval, defined as that including 95% of 194 control subjects, was 12-21 pmol/l. A limited overlap existed between euthyroid and hyperthyroid patients, but a larger one was seen between the euthyroid and hypothyroid population, the latter including subclinical hypothyroidism. IMx FT4 results agreed well when compared with those from two-step radioimmunoassays. The IMx FT4 technique gave rise to a low percentage of elevated results in patients being treated with heparin, but was undisturbed by autoantibodies to thyroxine and triiodothyronine which were present in one hypothyroid patient.

Adolescent↗
PubMed1991

Spiperone: a receptor ligand and/or a granular uptake tracer?

The accumulation of [3H]spiperone and [3H]dopamine was measured in striatum and pituitary gland slices of rat. Contrary to [3H]dopamine, [3H]spiperone storage was similar in striatum and pituitary gland. In addition, [3H]spiperone accumulation was not diminished by reserpine and tetrabenazine. These data show that spiperone is not subject to the granular uptake/storage mechanism and suggest that spiperone and its derivatives are specific ligands for dopamine receptors only.

Animals↗
PubMed1990

Iodobenzamide for in vivo exploration of central dopamine receptors: evaluation in animal models of supersensitivity.

Iodobenzamide is a promising agent to investigate D2 receptors by SPECT in living human brain. In this work, we have evaluated this radiolabeled compound in two animal models of D2 receptors supersensitivity. In the first model, rats were treated chronically with haloperidol during three weeks (S.C. injection of 0.5 mg/kg/day). One week after the last day of treatment, they were I.V. injected with 125I-IBZM. In vivo specific binding study showed a 45 percent increase of 125I-IBZM fixation in the striatum of treated rats. In a second step of experiments, animals were unilaterally lesioned by a stereotaxic injection of 6-OHDA in the substantia nigra, 23 days before receiving 125I-IBZM. Autoradiographic analysis of coronal brain sections showed a 38 percent enhancement of 125I-IBZM in vivo binding in the striatum on the lesioned side as compared to the contralateral intact side; this increase occurred in striatal lateral area. These data demonstrate that 125I-IBZM is convenient to detect alterations of dopamine D2 receptors in vivo in the rat. Thus IBZM labelled with 123I can be a very useful imaging agent for the exploration of D2 receptors in pathological situations.

Animals↗
PubMed1990

Iodoethylspiperone, a new potential agent for exploration of central dopamine D2 receptors: synthesis and preliminary in vivo study.

We synthesized a new spiperone derivative: iodoethylspiperone (IES) to perform dopamine D2 receptor exploration by SPECT. IES was prepared from a precursor: tosylethylspiperone, and characterized by i.r. and 1H-NMR analyses. [125I]IES was obtained with 80% yield. In vivo biodistribution in rats showed a high and specific uptake in the striatum. The uptake ratio between the striatum and the cerebellum reached a maximum value 4 h after injection (10.05 +/- 2.81). IES labeled with 123I should be a promising new agent to investigate D2 receptors in the living human brain.

Animals↗
PubMed1990

[125I]MIBG uptake and release in different regions of the rat brain.

Radioiodinated m-iodobenzylguanidine [( 125I]MIBG) and tritiated norepinephrine [( 3H]NE]) uptake and release were compared, in different regions of the brain of the rat. The classification of the regions according to uptake was the same for both tracers:striatum greater than hypothalamus greater than hippocampus greater than cortex greater than brainstem. Tetrabenazine (TBZ), a granular monoamine uptake inhibitor reduced the uptake in the different regions. The inhibition rate was higher for [3H]NE uptake than for [125I]MIBG. The spontaneous release was the same for [125I]MIBG and [3H]NE and was the lowest in the striatum. The K+ stimulated release of [3H]NE was more complete than the release of [125I]MIBG and was the most important in the striatum. From these results, it is inferred that MIBG enters the brain tissue via NE uptake mechanisms. It appears that MIBG is stored in the chromaffin granules, as NE, but also in the cytoplasm. A modified molecule derived from MIBG which would cross the blood-brain barrier, would then appear as a potential scintigraphic marker of monoamine uptake, storage and release.

3-Iodobenzylguanidine↗
PubMed1990

Diagnosis of medullary carcinoma of the thyroid (MCT) by calcitonin assay using monoclonal antibodies: criteria for the pentagastrin stimulation test in hereditary MCT.

A new calcitonin (CT) immunoradiometric assay, using anti-11-7 and anti-24-32 CT fragment monoclonal antibodies was evaluated and compared to classical RIA. The sensitivity was 2.5 ng/L, the normal basal level (n = 83) was lower than 10 ng/L, the response to pentagastrin stimulation in control subjects was absent in nine and between 10-30 ng/L in nine others. (mean, 15.4). In patients with renal failure the basal level was increased between 10-52 ng/L. In patients with medullary thyroid carcinoma (MTC; n = 28), the basal level was between 189-28,900 ng/L. A pentagastrin test was performed as screening for familial MTC in eight patients with confirmed MTC at subsequent surgery; the calcitonin peak was equal or greater than 38 ng/L. Large differences exist between CT levels measured by RIA and immunoradiometric assay. The latter method provides a greater sensitivity to pentagastrin test and allows a better identification of microcarcinoma in hereditary cases of MTC.

Adolescent↗
PubMed1990

[Scintigraphic assessment of pulmonary deposition of pentamidine administered by aerosol].

Isotopic techniques enable to determine the best conditions to aerosolize pentamidine as a preventive treatment of pneumocystis. An original labelling technique of pentamidine isethionate has led into a feasibility study of pentamidine scintigraphy in the monkey, and then to a clinical study. A tracer dose of 2 mg of pentamidine isethionate was diluted into 200 mg of pentamidine mesylate. An ultrasonic nebulizer (TV 6000) and a jet nebulizer (Venticis II) were first compared in four baboons. With the two nebulisers the curves of pulmonary kinetic activity showed a peak 10-15 minutes after the beginning of inhalation and then a plateau. With the ultrasonic TV6000 the pulmonary dose was on average 0.8 mg or 0.4% of the pentamidine aerosolized and the gastric contamination 3.1%. With the Venticis II compressed air apparatus the amount of pentamidine delivered to the deep lung was a mean of 4.2 mg or 2.1% of the aerosolized dose whereas the gastric contamination was only 0.5%. The delivery of the aerosol by the ultrasonic inhaler TV 6000 was then compared with two compressed air inhalers Venticis II and Respirgard II in four patients infected with HIV virus who were submitted to a preventative therapy against pneumocystis. With the ultrasonic TV 6000 the pulmonary dose was 0.8 mg or 0.3%-0.5% of the dose of pentamidine aerosolized and the digestive contamination was 3.1%. The performance of the two compressed air nebulizers Venticis II and Respirgard II were similar. The amount of pentamidine delivered to the deep lung was respectively 12 and 14 mg or 6 and 8% of the dose of pentamidine aerosolized and the digestive activity was 0.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1988

Comparison of MIBG and monoamines uptake mechanisms: pharmacological animal and blood platelets studies.

The uptake of MIBG, a scintigraphic agent widely used in the detection of APUD tumours, was studied with a pharmacological approach on an in vitro and an in vivo models. MIBG as well as norepinephrine (NE) was taken up by human blood platelets, a model for presynaptic nerve endings amine uptake, with a thermodependant mechanism. MIBG and NE uptake was inhibited by desimipramine and reserpine. However, MIBG but not NE uptake was inhibited by fluvoxamine, a serotonin (5HT) uptake inhibitor. This suggests that MIBG is a NE and also a 5HT uptake tracer which involves uptake one and vesicular storage mechanisms. In rats treated with 6-hydroxydopamine to induce a chemical sympathectomy, we observed an inhibition of uptake similar for MIBG and NE in the heart, the salivary glands and the spleen, but no effect was observed in the liver. Some clinical inferences to best investigate specific monoamine uptake are drawn from these results.

3-Iodobenzylguanidine↗
PubMed1988

MIBG and catecholamine storage in the brain: an in-vitro study.

The uptake and release of mIBG, a tracer of the monoamine uptake and storage function, were studied on superfused rat cerebral cortex sections. mIBG was taken up and released by a mechanism comparable to that of norepinephrine (NE), but this storage appeared to be less specific for mIBG than for NE. This implies that when mIBG is used as a scintigraphic tracer of monoaminergic synaptic vesicles, imaging should be delayed long enough to ensure release of the molecule from its nonspecific binding sites.

3-Iodobenzylguanidine↗
PubMed1988

Therapeutic effectiveness of iodine-131 MIBG metastases of a nonsecreting paraganglioma.

This case report describes the treatment of the bone metastases of a nonfunctioning sympathetic paraganglioma, with [131I]MIBG. After primary tumor excision and unsuccessful external radiotherapy, the patient received three therapeutic doses of [131I]MIBG, resulting in a reduction of the number and volume of metastases, and an improvement of the general condition. At 3 yr following [131I]MIBG therapy, the patient remained in remission. [131I]MIBG appears to be an efficient and safe agent for treating malignant sympathetic paraganglioma.

3-Iodobenzylguanidine↗
PubMed1988

[Osteocalcin and anomalies of cellular immunity in rheumatoid polyarthritis].

Spinal and peripheral skeletal demineralisation is sometimes observed in rheumatoid arthritis (RA). Numerous studies have shown the role of osteoclasts in its genesis, but few studies have been conducted to demonstrate a functional anomaly of osteoblasts. Synthesized by osteoblasts, osteocalcin enables to approach the osteoblastic activity, through titration of its serum level. In 31 patients suffering from erosive classical RA, we titrated the serum osteocalcin. In 9 cases, we found a definite decrease of the serum osteocalcin levels. There was a statistically significant difference between these 9 patients and the 21 others, in the presence of anomalies of the CD4/CD8 lymphocytic ratio, the presence of extra-articular manifestations, a high level of rheumatoid factors, class IgM, with an immuno-enzymatic technique. On the contrary, there was no difference regarding the mean duration of the RA course, the mean age, calcemia, and alkaline phosphatases level. Thus, in the course of severe clinical and immunological rheumatoid arthritis, an anomaly of cellular immunity was observed associated with abnormal serum osteocalcin levels. The exact mechanism of this decrease remains to be specified. Other prospective studies are necessary to confirm this preliminary research.

1-Carboxyglutamic Acid↗
PubMed1988

[Determination of plasma progesterone. Comparison of immunochemical luminescence (LIA) and radioimmunoassay (RIA)].

The authors describe an immunoassay technique of serum progesterone using a chemiluminescent tracer (LIA): progesterone aminobutylethylisoluminol 11-a-hemisuccinate (P-ABEI). The intrinsic characteristics of this technique were studied. The progesterone concentrations of 62 serum samples were simultaneously titrated using this LIA technique and a RIA technique. This LIA technique is quite practicable. The intra and inter-series ability to reproduce this test, and the sensitivities are excellent and comparable to those obtained with RIAs. There is a good correlation between the serum concentrations of progesterone determined by LIA and RIA (y = 1.12 x + 3.2; r = 0.95). A test with paired series did not demonstrate any significant difference (t = 0.67; 0.1 less than p less than or equal to 0.375). In conclusion, with a few technical adjustments (automated light meter, "coat tube"), this method could be perfectly suitable for titrations in a Biology laboratory.

Humans↗
PubMed1986

Radionuclide study of bronchial aspiration in intensive care newborn children.

Newborn children, fitted with tracheal prosthesis for mechanical ventilation, may present chronic pulmonary complications due to the repetition of silent aspirations following gastroesophageal reflux. We evaluated, in a newborn intensive care population, the frequency of such aspirations and the relationship between the different parameters and pathologies. This particular group of sick neonates cannot be moved, and as the hospital for the newborn is far from the Nuclear Medicine district, the patients cannot be scanned. We used a simple technique: the injection of a solution of 99Tcm-sulphur colloid in their gastric tube, and the measurement of the tracheal aspiration tubes' radioactivity. Thirty one children were tested; thirteen children (42%) had radioactive tracheal tubes. The study of the relationship between several parameters and our results, shows that the examination was generally positive when the maximal insufflation pressure value was low. Our results prove that silent aspirations are very frequent in such a population and that it will be perhaps useful to prevent them in a systematic way in order to save the neonates from developing pulmonary lesions.

Female↗
PubMed1986

An original method for submacroscopic metastases visualization in cases of cancer minimal residual disease.

Scintigraphic imaging due to its sensitivity is in many cases one of the most powerful techniques for demonstrating metastases. Severe limitations still exist in cancer when it is necessary to detect the presence of a few tumour cells in the residual minimal disease. In preliminary experiments it had been observed that an immunomodulator isolated from Nocardia bacteria (Nocardia Soluble Peptidoglycan Derivative: NSPD) electively bound to a model of activated macrophages. An hypothesis has been put forward that the enhanced detection of macrophages that are usually present in the vicinity or inside tumours should represent a polyspecific test for scintigraphy of a variety of metastases. NSPD radiolabelled with 99mTechnetium is not usable when injected intravenously due to its physiochemical properties. It has therefore been encapsulated into liposomes then administered via the respiratory tract as an aerosol. Amphiphilic properties, as well as its low molecular weight allow a rapid diffusion of NSPD in blood. Scintigraphy of metastases was possible from 1.5 to 6 hours after inhalation. The first stage of the study was carried out on 5 patients bearing known metastases (skin, lymph nodes, bone) from malignant melanoma that all were imaged with 99mTc-NSPD. The test was then applied to patients with a high risk of recurrent cancers (melanoma: 6, breast tumour: 7) based on the detection in their plasmas of high Lipid Associated Sialic Acid (LASA) concentrations. The association of these two sensitive techniques has resulted in the detection of very small metastases that were not seen using conventional scintigraphy; they were then confirmed histologically.

Aged↗