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Biomedical subjects

D Comar

Publications and source records attributed to D Comar.

At least 73 records · Page 4Linked to original sources

Brain uptake of 11C-methionine in phenylketonuria.

The brain uptake of 11C-methionine was studied in 26 children with classical phenylketonuria; one adult was used as a control. Labelled methionine uptake in brain was first measured during a low phenylalanine diet and again one week later after a load of phenylalanine. Ten children aged 1 to 30 months were studied twice at intervals of several months. In children having a phenylalaninemia less than or equal to 0.3 mumoles . ml-1, a decrease in methionine brain uptake was observed with increasing age, with the largest change occurring during the first year of life. After the phenylalanine load, a mean increase in phenylalaninemia by a factor of ten was accompanied by a mean decrease in brain methionine uptake by a factor of two while blood methionine remained unchanged. Brain activity curves increased with time for children younger than one year and having phenylalaninemia less than 0.6 mumoles . ml-1. After the age of 2 most patients had a decreasing curve regardless of the blood phenylalanine level. This study indicates that 11C-methionine brain uptake may be taken as an index of blood barrier permeability to essential amino acids, and of brain maturation. The results obtained suggest that an increase in phenylalaninemia to levels greater than 0.6 mumole . ml-1 induces a modification in brain uptake of amino acids, primarily during the first two years of life.

Adult↗

Application of in vivo activation analysis to the compartmental study of sodium in the hand.

Sodium kinetics were studied in the hands of 14 subjects by local in vivo neutron activation analysis. Hands were irradiated with 252 Cf sources giving absorbed doses of 8 cGy. The variation in 24Na radioactivity was plotted against time, and each curve fitted to a function that was the sum of two exponentials. Two pools were identified, one corresponding to fast turnover, with a half-life of about one hour, the other to a slower turnover process with a half-life averaging 79 h if the calcium concentration of the hand bones is normal, and 35 h if it is subnormal. The mean ratio of calcium to slowly exchangeable sodium is estimated to be 47.7, and the ratio of quickly exchangeable sodium to slowly exchangeable sodium to be 0.65. These various parameters should be of interest in bone pathology.

Activation Analysis↗

Noninvasive tomographic study of cerebral blood flow and oxygen metabolism in vivo. Potentials, limitations, and clinical applications in cerebral ischemic disorders.

The non-invasive continuous inhalation technique of C15O2 and 15O2 coupled with positron emission tomography (PET) provides brain images that are thought to represent local cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Experimental studies in baboons have confirmed that C15O2 inhalation allows tomographic measurement of CBF. The numerous difficulties involved in PET absolute quantitation are stressed, as well as some limitations inherent to the 15O inhalation model. However, the values for local CBF, OEF and CMRO2 obtained in normal young subjects are satisfactory in view of the above-mentioned limitations. The clinical application to recent cerebral infarction has allowed two opposite types of flow-metabolism uncoupling to be identified, which appear to be often predictive if tissue prognosis. The time course of spontaneous changes in CBF and OEF within the infarct is also described. Our studies have, in addition, revealed the previously unknown phenomenon of "crossed cerebellar diaschisis" in supratentorial infarction. Lastly, a state of chronic watershed ischemia, potentially reversible by surgical revascularization, has been identified as presumably involved in the progression of watershed necrosis. The clinical potentials of this method appear considerable.

Adolescent↗

A new radioisotope for lung ventilation studies: 19-neon.

Neon 19, 17-second positron-emitting radioelement, is produced continuously by 23MeV alpha particle bombardment of oxygen. For a 12 muA particle current the method of preparation described delivers 14 mCi of neon 19 per min to the functional exploration room. The radiochemically pure radioactive gas is diluted in air and breathed continously by the patient lying under a positron tomographic camera. The regional lung ventilation distribution is obtained on 2 cm thick sections of organ with a transverse resolution of 17 mm. Quantification of the ventilation output per unit lung volume is contemplated.

Heart Ventricles↗

A new generator for ionic gallium-68.

To meet the needs created by the rapid development of positron tomographic techniques, a new Ge-68 leads to Ga-68 generator has been developed. By elution under reduced pressure, this tin dioxide/1 N HCl generator provides a sterile solution of Ga-68 in ionic form, ready for use in the preparation of many radiopharmaceuticals. Since the Ga-68 recovery yield is high (75--80%) and the elution time very short (less than 2 min), these products possess maximum activity. Owing to its very slight Ge-68 leakage (less than 0.0002% per elution), the tin dioxide/HCl generator is long-lasting and, more importantly, the radiotoxicity of the labeled derivatives is kept to a minimum. The ionic Ga-68 obtained in this way has been used to label several radiopharmaceuticals.

Gallium Radioisotopes↗

The physical performances of a single slice positron tomographic system and preliminary results in a clinical environment.

Metabolic phenomena can be studied and measured non-invasively using positron emitting radionuclides and a suitably adapted tomographic system. The choice of a single slice ring camera is justified by its physical performance, which is presented here and discussed. A series of measurements with geometrical phantoms and analytical simulations have been performed to determine the critical characteristics of the system. This has permitted optimization of certain parameters enabling very interesting clinical results to be obtained at SHFJ, particularly in the area of cerebral physiopathology. In addition, the potential of obtaining absolute quantitative values of regional activity is presented. The calibration of the regional activity is presented. The calibration of the system, spatial non-stationarities, and attenuation correction, which represent the main sources of error, are considered in detail. A precision of the order of 10% should be obtainable. Such a quantitation method has been successfully applied to the in vivo study of the regional extraction of cerebral oxygen.

Brain↗

Simple, fast preparation of gallium-68-labelled human serum albumin microspheres.

Following a study of the main factors involved in the 68-Ga labelling of human serum albumin microspheres (H.S.A.M.), especially methods of production and preparation of active solution and conditions of radioelement fixation on the protein support, the practical details of a fast technique (60 min) based on the process described by Hnatowich are presented. This method gives high labelling yields (93 +/- 3%), and after washing of the microspheres leads to a radiopharmaceutical product almost without free 68Ga (less than 2%). The spheres ready for use carry a total radioactivity corresponding to about 35%, including decay, of the activity originally recovered in the generator eluate and to more than 98% of that, found in the final suspension. The labelled product is sterile, non-pyrogenic and non-toxic. When it is injected in animals by left ventrical catheterization the uptake rates in the heart, lungs, spleen, left kidney and right kidney are similar to those observed with reference 85Sr-labelled carbonized microspheres. This radiopharmaceutical, easy to prepare and having excellent biological and nuclear properties, seems ideally suited for the scanning of organs by position emission tomoscintigraphy.

Animals↗

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.

Adolescent↗

[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.

Carbon Radioisotopes↗

In vivo analysis of bone calcium by local neutron activation of the hand: results in normal and osteoporotic subjects.

Mineral loss from bone can be measured accurately and reproducibly by neutron activation of the hand bones using a 5-min irradiation (10(6) n/cm2-sec) with two 200-microgram sources of Cf-252. The hand dose is 7.5 rad equivalent and the dose to the rest of body is 1.5 mrem. Controls (132) and osteoporotic patients (45) were compared. Between ages 20 and 60 the control group showed a bone calcium concentration of 0.177 +/- 0.025 g/cm3, independent of age. Between 60 and 70 the content remained unchanged in men but declined in women to 0.15 +/- 0.2 g/cm3. In all age groups osteoporotic patients in general showed lower calcium content. Comparison of our findings ("Ca") with estimates of bone mineral content obtained by photon absorptiometry ("BMC") yields 0.07 Ca + 0.262 (r = 0.87). Activation analysis of hand bone appears more precise than BMC for the monitoring of bone-mineral loss in each individual and as a measure of treatment efficacy.

Activation Analysis↗

Carbon 11 labeling of the psychoactive drug o-methyl-bufotenine and its distribution in the animal organism.

A methylated derivative of serotonin, O-methyl-bufotenine has been labeled with 11C on the two methyl groups of the amine function. In order to avoid the cyclization which occurs during the Eschweiler-Clarke synthesis, we adopted a milder methylation procedure, based on Borch's method using [11C]formaldehyde and sodium cyanoborohydride. Several tens of millicuries of injectable product could be obtained in 50 min in a perfectly pure state and having a specific radioactivity of 50 to 100 mCi/mumol. The distribution study of O-methyl-bufotenine in the mouse and rabbit showed an accumulation of significant quantities of the compound in the brain, kidneys, lungs and liver. The study of the rapid kinetics of this hallucinogenic molecule is compatible with labeling by 11C, having a period of 20 min. The use of O-methyl-[11C]bufotenine to detect serotonin receptors in vivo in mental diseases, is considered.

Animals↗

[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].

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.

Aged↗