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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.

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.

The aim of this study was to see if an enhanced myocardial stiffness is an inevitable consequence of the increase in cardiac mass and to analyze the effects of beta-adrenergic blockade on this parameter. The DOCA-salt model of hypertension was used to induce cardiac hypertrophy in the rat. After 6 weeks, the hearts of the DOCA-salt-treated animals were hypertrophied by 67%, and the left ventricular weight, the left ventricular/body weight ratio and the left/right ventricular weight ratio were similarly increased. Isolated hearts were retrogradely perfused at a constant flow of 15 ml/min/g tissue. Contractile parameters were recorded using an intraventricular balloon whose volume was manually adjusted. For each heart, a sequence of three systolic and diastolic pressure-volume curves were constructed: in Krebs alone, after addition of 10(-6) M of propranolol, and after KCl-arrest. In spite of a pronounced degree of hypertrophy, the DOCA-salt hearts had a normal diastolic pressure-volume curve and both the chamber and tissue stiffness constants were not modified. This result indicates that a depressed compliance does not necessarily accompany hypertrophy, especially in a DOCA-salt model in which the collagen content of the heart is unchanged. The systolic pressure-volume curve was greatly modified and shifted to the left indicating an enhanced capacity of the hypertrophied heart to generate force. This increase persisted even when the systolic pressure has been divided by the heart weight. beta-Blockade slightly depressed the contractility of the isolated heart at pharmacological concentrations. At high concentrations, cardiac dilatation was induced. This enhancement in ventricular distensibility had no consequences on diastolic compliance constants. It is thus concluded that, during cardiac hypertrophy, the changes in passive stiffness of the ventricle are more related to collagen content than to the cardiac mass and that beta-adrenergic blockade has no effect on the passive properties of the ventricle.

The bone metastases of a malignant, non-secreting paraganglioma were treated with [131I]metaiodobenzylguanidine (131I-MIBG) over a 10-year period. Initial treatment (131I-MIBG: 9.6 GBq) resulted in a decrease in the number of bone metastases from 16 to 2. At three years, a relapse with primary tumor regrowth and liver metastasis was again treated with 131I-MIBG (22.2 GBq). A decrease in the number of bone metastases and MIBG uptake was again observed.

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.

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)

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.

The concentration of thyroxine-binding globulin in the serum can now be measured by a simple and specific radioimmunoassay. Triiodothyronine uptake and measurement of total thyroxine have been combined to yield a free thyroxine index which has been found to correlate with the clinical state of the patients. An estimate of the free thyroxine concentration, as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays, provided a good correlation with the free thyroxine index and the thyroxine: thyroxine-binding globulin ratio. However, the thyroxine: thyroxine-binding globulin ratio is inaccurate when thyroxine-binding globulin concentrations are high or low.

This report describes the comparison between two adrenal medulla imaging agents, mIBG and I-CPP. Biodistribution demonstrated an early and preferential uptake by both adrenal glands and heart and then storage in the adrenal gland of both agents, however I-CPP is less stable in vivo than mIBG. Reserpine depletion study in rat indicated that the I-CPP and mIBG uptake mechanisms are not similar.

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.

In this article, which is a preliminary report, the authors determined amniotic fluid levels of alpha-I-antitrypsin, orosomucoid, transferrin and alpha-fetoprotein during complicated pregnancies with gestational ages of 31 to 42 weeks. These levels were compared with those observed during normal pregnancies. The clinical value of the variations of the glycoprotein levels is discussed.

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.

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.

A total of 122 cases of various neurological diagnoses (among which 72 cerebral infarcts, 7 intracerebral hematomas and 38 intracranial tumors) had two separate brain scans, performed within 48 hours of each other after the administration of pertechnetate and technetium stannous pyrophosphate. The comparison of the resulting seans indicates that, in addition of an osseous accumulation, the pyrophosphate localizes greatly in ischemic cerebral lesions, especially those observed during the second week of evolution. It seems that the uptake of pyrophosphate reflects the area of anaerobic changes whereas the accumulation of pertechnetate depends on the disruption of the blood brain barrier. The scintigraphic diagnostic of cerebral infarctions is greatly improved.

For animal experimentation, the 95m and 96 technetium isotopes offer many advantages over technetium-99m. Their long physical half-lives and the emission of extranuclear electrons of low penetrating power make it possible to obtain autoradiograms of a great precision. The uptake of technetium stannous pyrophosphate by the epiphyseal plate was studied using liquid-emulsion microautoradiography, 3 hr after i.v. injection into 10-week-old rabbits. Microautoradiograms showed a well-defined and rather specific pattern of localization with intense uptake beneath the epiphyseal disk on the extremities of the vascular buds and a lack of accumulation in the cartilage, whether calcified or uncalcified. In the metaphysis, the label was located where new bone was being laid down and also over the cytoplasm of osteoclasts. We deduce from these results that in normal bone the general distribution of this tracer reflects mainly the arrangement of the blood supply, but the specific sites of accumulation are the bone-forming surfaces and the active resorbing osteoclasts.

Autoradiograms were performed on brain slices, 3 h after 99mTc-pertechnetate injection, and 24 h after previous treatment with stannous pyrophosphate. On macroautoradiograms, the radioactivity was focused entirely upon plexus areas. Silver grains were predominantly overlying the cytosol of brush border cells; less than 10% of the total plexus radioactivity was found in vascular structures. These findings suggest that a possible metabolic phenomenon exists rather than a passive distribution.

The authors have set up a thyroxine-binding-globulin radio-immunoassay in blood serum. The standard used has been determined by gravimetry, its maximal thyroxine-binding capacity is 0,96 mole of thyroxine per mole of TBG. Serum concentration of TBG has been measured in 159 euthyroid normals. The mean value of the concentration is 20 mg/l.

In a patient who had undergone surgery for a medullary carcinoma of the thyroid, and with multiple hepatic metastases and severe diarrhoea, prostaglandins PGE1, PGE2, and PGF2alpha measured in peripheral venous blood and hepatic venous blood were normal in level and closely comparable, i.e. without gradient. Arachidonic acid, a PGs precursor, labelled with Iodine 131 was not taken up in the plaques of hypofixation seen with bengal rose and technetium sulphate. Finally, aspirin and indomethacin failed to relieve the diarrhoea. It is suggested that PGs were not secreted by the hepatic metastases and could not therefore be considered responsible for the diarrhoea.

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.

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.

Renin Plasmatic Activity (R.P.A.) was increased in three cases of Pheochromocytoma Plasmatic aldosterone (A), measured in one patient, was high in the supine position and increased considerably in orthostatism. This was not observed with the R.P.A.7. Urine Tetra Hydroaldosterone (T.H.A.) was increased in two of the three patients and this increase corresponded to the Pheochromocytoma in which the V.M.A. concentrations were the highest. P.R.A., T.H.A. and V.M.A. regained normal values after surgery. We suggest that there is a certain parrallelism between the increase in the excretion of A. and the importance of the catécholamine release from the Pheocchromocytoma.

Nine sera with falsely elevated results in a TSH radioimmunoassay were studied. Sera dilution and gel filtration showed that the immunoreactive TSH was different from the standard and labeled TSH. It coeluted with the immunoglobulin fraction of the serum. Rabbit serum decreased or emphasized the artifact according to the dose. Falsely elevated results appeared only in radioimmunoassays using a double antibody method for the separation of free and bound labeled hormone. FSH, LH, and beta HCG radioimmunoassays using the double antibody method underwent the same disturbance as the TSH assay in these patients. Our results suggest that the artifact may be due to the presence in certain human sera of anti-rabbit IgG antibodies, interfering in the radioimmunoassay by inhibition of the binding of first and second antibodies.

Fine-needle aspiration cytology was performed in two cases of intra-abdominal tumors, one from retroperitoneal lymph nodes and one from a cryptorchid testis. The cytological diagnosis was consistent with seminoma in both cases. Cytological features included uniform neoplastic malignant cells with round nuclei and nucleoli. The cytoplasm, easily observed on May-Grünwald-Giemsa-stained smears, contained large vacuoles or lacunes filled with glycogen. Alkaline phosphatase activity was strictly located to one cytoplasmic area of the cells. This cytological and cytoenzymatic pattern is different from that observed in other intra-abdominal tumors, including adenocarcinoma, large-cell lymphoma, and embryonal carcinoma.

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.

Based on experience of the last decade including 18 patients, the imaging procedures of medullary thyroïd carcinoma are reviewed. Ultrasonography of the neck is the most contributive for the locoregional expertise, in the preoperative period. All of the classical imaging procedures are useful in looking for the metastasis: namely bone scintiscan, liver ultrasonography, computerized tomography of the mediastinum. Associated parathyroid adenoma and pheochromocytoma are visualized respectively by technetium thallium subtraction scan and meta-iodobenzylguanidine scintigraphy. In the near future, immunoscintigraphy of calcitonin secreting tumors will be developed.

Rabbit alpha-1-M and alpha-2-M labelling was carried out in vitro with 131I and in vivo with 75-Seleno-methionine in order to determine the half-life of these proteins. alpha-2-M catabolism is faster than the alpha-1-M one. This result is the same when these proteins were obtained from a plasma of a rabbit exhibiting an inflammatory reaction though their half life was shorter.

The distribution of C-cells in the thyroid gland of the gerbil (Meriones inguiculatus) was studied on serial sections in the cranio-caudal direction. C-cells were visualized by immunofluorescence with an anti-calcitonin immune serum. A very heterogeneous distribution was found. C-cells first appear in the posterio-interior position. Then they progressively occupy the whole posterior part and finally are confined to the posterio-exterior position. No C-cells at all were detected in the upper and lower poles. According to the species, there is a wide variation in the relative distribution of C-cells in the thyroid gland. Our results add to the information available about the distribution of C-cells and its bearing on phylogenic evolution.

A relationship is proposed for calculating the concentration of free serum thyroxine using the measured values of thyroxine and thyroxine-binding globulin total concentrations. This calculation has been performed on a population of 335 patients. A good discrimination of the different thyroid diseases has been obtained.

Radiolabeled anti-calcitonin (CT) immunoglobulin fragments (131I-anti-CT F(ab')2) and meta-iodobenzylguanidine (131I-mIBG) were injected into nude mice with a transplanted medullary thyroid carcinoma (MCT). 131I-Anti-CT F(ab')2 proved to be unsuitable for MCT scintigraphic imaging. However, a high mIBG uptake was observed in MCTs, but not in control tumors (mesothelioma). The uptake of mIBG was not modified by the presence of reserpine or pentagastrine. These results are discussed, and it is suggested that mIBG could be an APUD-system marker.

In order to evaluate the frequency of elevated circulating calcitonin in patients with bone metastasis plasma calcitonin level was measured in 32 patients with breast carcinoma with and without bone metastasis. Calcitonin was found in normal ranges in all patients without metastasis. In patients with bone metastasis, 4 had normal level, 2 were found with elevated calcitonin. Our results suggest that elevated calcitonin is related to the presence of bone metastasis but is not a constant finding in these patients.

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.