Dopaminergic receptor sites in human brain: positron emission tomography.

Positron emission tomography (PET) and 11C-labeled pimozide were used to study the dopaminergic (DA) receptor sites in the human striatum by comparing the latter with the cerebellum, which lacks DA receptors. Although 11C-pimozide concentration was not different in these two brain structures up to 53 minutes after IV injection (thus implying large nonspecific binding), a significant retention of radioactivity in striatum relative to cerebellum was found in controls but not in subjects pretreated with the unlabeled competitor haloperidol. This suggests that the striatal retention seen in controls was due to specific binding of 11C-pimozide to DA receptor sites, whereas prior occupation of the receptor sites by the unlabeled competitor was achieved in pretreated subjects.

Mössbauer spectroscopy study of iron overloaded livers.

Absorption 57Fe Mössbauer spectra have been carried out directly on fresh or lyophylized tissues of liver with either normal iron depot or iron overload. Two types of overloading have been studied: primary iron overload due to an excessive intestinal iron absorption and secondary iron overload (hemosiderosis) produced in beta-thalassemia patients by hypertransfusional therapeutics. The Mössbauer spectra, at room temperature, 77 and 4.2 K, on normal liver samples, are typical for the ferritin-hemosiderin compounds. In the spectra, performed on hemosiderosis liver samples, there appears, in addition to ferritin and hemosiderin, a new iron molecular environment, typical of high spin ferric iron and characterized by a superparamagnetic behaviour which begins at high temperature (above 77 K). This new component does not show up in the primary iron overload cases and seems characteristic of the physiological process which induces the iron overload.

Mössbauer spectroscopy and perturbed angular correlation studies of the rare-and alkaline-earth bone uptake.

Emission Mössbauer spectra and Perturbed Angular Correlation measurements have been performed on samples of mineral bone powder labelled with 161Tb3+ or 133Ba2+ ions after either in vitro absorption or uptake by metabolic pathway. The study of these hyperfine spectra, compared with those carried out when 161Tb or 133Ba are situated in either hydroxyde lattice or phosphate one, shows that the uptake modes of rare-and alkaline-earth ions on the bone matrix are different. The rare earth ion seems to be absorbed on the surface bone in an environment of hydroxyl groups similar to the structure of a rare earth hydroxyde. The alkaline earth ion bone uptake appears more complicated and would make according to the following process : at first, surface absorption on the hydroxylapatite in a hydroxyde environment and then cationic exchange with the calcium phosphate groups into bone crystals.

Pulmonary extraction of C-11 chlorpromazine, measured by residue detection in man.

Uptake of C-11 chlorpromazine (CPZ) was measured to evaluate the nonrespiratory function of lung in patients. A multiple-indicator dilution technique was used with external detection. Following intravenous bolus injection of C-11 CPZ, with In-113m transferrin as an intravascular reference molecule, counts were recorded with a scintillation camera using two energy windows. The residue functions, R(t), for C-11 CPZ and In-113m transferrin were plotted against time for selected areas of interest, and the CPZ area-weighted extraction, E(t), was computed for the same areas every 250 msec using the formula: E(t) = [RT(t) - RR(t)]/[1 - RR(t)], where RT and RR are the normalized residue functions for CPZ and transferrin, respectively. The initial extraction was 90 +/- 5% in four normal subjects and 64 +/- 7% in six patients with chronic obstructive lung disease (C.O.L.D.), these values being significantly different (p less than 0.001). The large initial extraction of CPZ in a single passage through the pulmonary vasculature resulted from a fixation to membranes, due to its high liposolubility. The lower extraction seen in patients with C.O.L.D. was explained by weaker fixation to lung tissue.

[11C]methionine pancreatic scanning with positron emission computed tomography.

By the use of [11C]methionine and positron computed tomography (PCT), images of the pancreas were obtained in 32 patients. The injection of between 10 and 20 mCi of this product enables four to six transverse sections to be obtained. Seventeen of the patients studied had no exocrine pancreatic disease, and in all these cases the pancreas was clearly visible. In four cases of pancreatic carcinoma and one of retroperitoneal tumor, there were abnormalities visible. In five cases of chronic pancreatitis, no pancreatic uptake was observed. In a sixth case, concentration was visible, but only in the head of the pancreas. One case of acute pancreatitis, which showed no concentration during the acute phase, returned to normal after recovery. When visible, the pancreas was easily located and distinguishable from the intestinal image, except in two cases that were uninterpretable for technical reasons. No false positive or negative was observed, but a differential diagnosis between cancer and pancreatitis was impossible.

X-irradiation effect on human red cells: hemoglobin study by Mössbauer spectrometry.

This work is a study of the radioinduced transformations undergone by intraglobular hemoglobin. Mössbauer spectrometry allows us to study in a wide range of doses the effect of X rays on deoxyhemoglobin as well as on oxyhemoglobin. Using this technique we have shown large differences between these two derivatives of hemoglobin. Deoxyhemoglobin leads to the formation of only one ferric nonheme compound while oxyhemoglobin produces this same compound as a last step after intermediary production of deoxyhemoglobin, methemoglobin, hemichromes, and hemochromes. We have also found that heat incubation and X rays have a similar effect on HbO2 except for the dissociation, which is absent in heat incubation. We have found a value for the energy needed for such a radiodissociation of HbO2 similar to that given by other authors utilizing other methods. Finally, we propose some explanations for the formation of the different compounds involved based on structural considerations.

Time differential perturbed angular correlation (TDPAC) studies of the 133Ba ion uptake in bone crystals.

TDPAC measurements of the 356-81 keV gamma-ray cascade resulting from electron capture decay of 133Ba have been performed at room temperature on BaCl2 (aqueous solution and polycrystalline powder), and on samples where the 133Ba nucleus is bound to bone powder, and also to synthesised hydroxylapatite, all after absorption in vitro. As expected, the angular correlation is not perturbed in the solution. However, in the polycrystalline chloride the time dependence of the anisotropy of the cascade of 133Cs nuclide indicates that the decaying nucleus undergoes electric interactions due to different electric field gradients acting at the site of the nucleus. In 133Ba-bone powder the results show a static quadrupolar interaction differing with the absorption contact time during sample preparation, indicating that depth of 133Ba ion fixation in the bone crystal is dependent on this contact time. These results seem to be confirmed by the TDPAC measurements performed on 133Ba-hydroxylapatite samples where the contact times for absorption of active-ion 133Ba and hydroxylapatite in suspension were very different.

Brain distribution and kinetics of 11C-chlorpromazine in schizophrenics: positron emission tomography studies.

The positron emitter 11C (20 minutes half-life) permits the labeling of chlorpromazine (CPZ) and the study of its distribution in humans by external counting. Trace amounts of 11C-CPZ were injected intravenously into 22 schizophrenic patients all untreated for several months with neuroleptics. The brain uptake was 6.04 +/- 1.6% of the injected dose 15 minutes after the injection, and it remained constant for 45 minutes. By positron emission tomography, the drug distribution was shown to be in the gray matter, and such structures as the cortex, caudate nucleus, thalamus and putamen could be identified. This new methodology will be helpful in studying specific receptors in humans in a noninvasive way.

[Tomographic study in humans of blood flow and oxygen consumption of the brain by continuous inhalation of oxygen 15. Preliminary findings in cerebral ischemic accidents]. / Etude tomographique, chez l'homme, du débit sanguin et de la consommation d'oxygène du cerveau par inhalation continue d'oxygène 15. Résultats préliminaires dans les accidents ischémiques cérébraux.

Transverse axial tomographic imaging of regional cerebral blood flow (rCBF) and regional oxygen extraction fraction (rOEF) were obtained in 13 patients hospitalizedfor ischemic strokes (eleven middle cerebral artery territory infarcts, one capsular or pontine lacune, one transient hemispheric attack) by continuous inhalation of 15O2 and C15O2 to equilibrium and exclusive detection of the gamma rays emitted in coincidence by means of a tomograph for positron emitting agents. In the transient ischemic attack and in the case of lacune the rCBF and the rOEF images were found to be normal, and they were abnormal in all cases of middle cerebral artery territory infarcts. In recent infarcts, rOEF was always strikingly decreased in the clinically suspected area, whilst the rCBF was either decreased, normal or increased. In infarcts older than 30 days rCBF was always clearly decreased over the clinically suspected area whilst rOEF was in most cases normal or only slightly decreased. These results are briefly discussed. Some practical and theoretical limitations of this method are mentioned. The potential of the present technique appears great however, since it is possible to simultaneously visualize in tomographic fashion the blood flow and the oxygen metabolism in areas of the brain that are of small volume, and however deep they are. A quantification of these parameters is presently under investigation, as well as the verification of the theoretical model on which such method is based. The non-invasiveness of the present method, the feasibility of repeating it at regular intervals of time, and the possibility of measuring the immediate effects of a given therapeutic mode on the regional metabolism of brain all constitute further advantages whose action apply preeminently in the field of the cerebral ischemic diseases.