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Biomedical subjects

A Syrota

Publications and source records attributed to A Syrota.

At least 145 records · Page 8Linked to original sources

Brain tumor protein synthesis and histological grades: a study by positron emission tomography (PET) with C11-L-Methionine.

Brain protein synthesis may be evaluated in vivo by a PET three compartment methionine model. 14 human brain tumor patients were studied. Protein synthesis rate (PSR) was increased in any glial tumor even in low grades, but this increase was statistically more important in anaplastic tumor. Radiotherapy action was evaluated in two patients. Local tumoral PSR was reduced to normal brain PSR after treatment. No difference was seen in normal cortex contralateral to the lesion between pre and post radiotherapy examination. 11 C-L-Methionine incorporation measured by PET looks as a very sensitive method for studying tumor metabolism and treatment effects.

Adult↗

Use of 11C-triphenylmethylphosphonium for the evaluation of membrane potential in the heart by positron-emission tomography.

The membrane potential in cells can be estimated by electrophysiological techniques and biomedical methods using lipophilic cations labelled with 14C. However, these techniques cannot be applied to the human heart. In this study a lipophilic cation, triphenylmethylphosphonium (TPMP), was labelled with carbon-11 with the purpose of investigating its suitability for the estimation of membrane potential in vivo. A biodistribution study in mice and rats showed significant uptake of the cation in the heart a few minutes after IV injection which remained constant for 60 min. In vivo study by positron-emission tomography showed that after IV injection of 11C-TPMP in the dog, activity rose almost immediately in the myocardium and then remained constant for 60 min. A rapid injection of KCl (greater than 40 mg/kg) 20 min after injection of 11C-TPMP led to an instantaneous fall in myocardial 11C-TPMP concentration. Membrane potential (delta psi), calculated from the TPMP distribution ratio between intracellular and plasma water space by the Nernst equation, was estimated at -148.1 +/- 6.0 mV for the dog heart. This value reflected both cell membrane potential and mitochondrial membrane potential and, thus, the energy state of the myocardial cells.

Animals↗

Peripheral-type benzodiazepine receptors in the living heart characterized by positron emission tomography.

The presence of specific benzodiazepine binding sites in the hearts of dogs and human beings was demonstrated in vivo by a noninvasive method, positron emission tomography (PET). An antagonist of the peripheral-type benzodiazepine binding site, PK 11195, was labeled with carbon-11, a short-lived positron emitter. When injected at high specific activity, 11C-PK 11195 was concentrated in the myocardium. As increasing amounts of unlabeled PK 11195 were added to the radioactive ligand, the myocardial ligand concentration was proportional to myocardial regional perfusion up to quantities of 40 nmol/kg body weight. Above 40 nmol/kg the ligand concentration reached a maximum value (6000 pmol/cm3), which could be considered as the total number of binding sites per unit heart volume. The specificity of 11C-PK 11195 binding to canine heart was demonstrated from a study on the inhibition of binding for radioligand by an excess of several agonists or antagonists of benzodiazepine receptor. The distribution and specificity of 11C-PK 11195 was similar in dogs and in human beings. PET thus opens the way to the investigation of the peripheral-type benzodiazepine receptor in a clinical situation, since it has recently been shown that this receptor could be coupled to the calcium channel in the heart.

Animals↗

Production of high specific activity 123I for protein iodination for medical use.

Iodine-123 is produced via xenon-133 by irradiation of a sodium iodide target with 108 MeV deuterons from the synchrocyclotron of IPN. The on-line production method is described. The specific activity of the iodine is determined by neutron activation analysis and by a radioimmunological method. The conditions labelling different proteins (insulin, angiotensin) are given and also the purification method to obtain a product ready for injection to patients.

Angiotensins↗

Tomographic mapping of brain intracellular pH and extracellular water space in stroke patients.

Functional images of regional intracellular pH (pHi) and of fractional volume of extracellular water (FVECW) were obtained in 10 patients with recent hemispheric infarction (between 10 and 19 days after onset of symptoms) using positron emission tomography (PET). The volume of extracellular water relative to that of total water was evaluated in each pixel of the PET scan 7-8 h after injection of 76Br. The pHi image was calculated from the data obtained after injection of [11C]5,5-dimethyl-2,4-oxazolidinedione and from the FVECW image. Regional CBF, oxygen extraction, and oxygen metabolism were also measured in the same patients. In normal hemisphere, mean +/- SD values for FVECW and pHi were 0.12 +/- 0.01 and 6.86 +/- 0.11, respectively. FVECW was increased in the infarcted area in most patients. pHi was increased in the infarct in seven patients and unchanged in three. The increase in pHi was not correlated with changes in FVECW, CBF, or CMRO2, but there was a significant correlation with the decrease in oxygen extraction fraction in the same region. Thus, the decreased H+ content in the infarcted area was correlated with the occurrence of perfusion in excess of metabolic demand. An alkaline shift in pHi enhances the glycolysis rate and could explain why the glucose metabolism is less affected than the oxygen metabolism in recent cerebral infarction. The pHi measured in the infarct could represent mainly the pHi of phagocytic cells that use aerobic glycolysis to synthesize hydrogen peroxide.

Adult↗

Muscarinic cholinergic receptor in the human heart evidenced under physiological conditions by positron emission tomography.

The muscarinic receptor was studied in vivo in the human heart by a noninvasive method, positron emission tomography (PET). The study showed that the binding sites of 11C-labeled methiodide quinuclidinyl benzilate [( 11C]-MQNB), a muscarinic antagonist, were mainly distributed in the ventricular septum (98 pmol/cm3 of heart) and in the left ventricular wall (89 pmol/cm3), while the atria were not visualized. A few minutes after a bolus intravenous injection, the concentration of [11C]MQNB in blood fell to a negligible level (less than 100th of the concentration measured in the ventricular septum). When injected at high specific radioactivity, the concentration of [11C]MQNB in the septum rapidly increased and then remained constant with time. This result was explained by rebinding of the ligand to receptors. It was the major difference observed between the kinetics of binding of [11C]MQNB to receptor sites after intravenous injection in vivo and that of [3H]MQNB to heart homogenates in vitro. The MQNB concentrations in the ventricular septum of different individuals were found to be highest when the heart rate at the time of injection was slow. This result suggests that the antagonist binding site is related to a low-affinity conformational state of the receptor under predominant vagal stimulation. Thus, positron emission tomography might be the ideal method to study the physiologically active form of the muscarinic acetylcholine receptor in man.

Atropine↗

Kinetics of in vivo binding of antagonist to muscarinic cholinergic receptor in the human heart studied by positron emission tomography.

Positron Emission Tomography (PET) was used to analyse in vivo antagonist binding to human myocardial muscarinic cholinergic receptor. The methiodide salt of the muscarinic antagonist, quinuclidinyl benzilate (MQNB), was labeled with the positron emitter, Carbon-11, and injected intravenously to 8 normal subjects. 11C-MQNB concentration was determined in vivo in the ventricular septum from 40 cross-sectional images acquired at the same transverse level over a period of 70 minutes. In 4 subjects, various amounts of unlabeled atropine were rapidly injected at 20 minutes to study whether atropine competitively inhibited MQNB. The kinetics of binding of 11C-MQNB were not the same in vivo and in vitro. The apparent dissociation rate of 11C-MQNB in vivo was much slower (by 1 to 2 orders of magnitude) than that observed in vitro with 3H-QNB. After atropine injection, 11C-MQNB dissociated from its binding sites at a rate that apparently depended on the amount of atropine present. 11C-MQNB kinetics were analysed with a mathematical model which assumes the existence of a boundary layer containing free ligand in the vicinity of the binding sites. The dissociation rate of the radioligand depends on the probability of its rebinding to a free receptor site.

Atropine↗

Tissue acid-base balance and oxygen metabolism in human cerebral infarction studied with positron emission tomography.

Nine patients who had suffered strokes were examined between 10 and 34 days after onset using positron emission tomography. DMO labeled with carbon 11 was used to evaluate brain acid-base balance, and the oxygen-15 inhalation technique was used to measure regional cerebral blood flow, the oxygen extraction fraction, and cerebral metabolic rate for oxygen. [11C]DMO concentration and oxygen metabolism variables were measured in the infarcted area and in the symmetrical region in the contralateral cerebral hemisphere. [11C]DMO concentration was found to be unchanged or slightly increased in five cases and markedly increased in four cases. The apparent increase in tissue pH can be explained by the presence of a large extracellular fluid space with a pH nearly identical to that of brain plasma, or by an increase in intracellular pH, or by both phenomena. The change in [11C]DMO concentration in the infarcted area relative to that in the normal tissue was independent of the change in blood flow. Cerebral metabolic rate for oxygen was decreased in all cases. The increase in [11C]DMO concentration in the infarcted area was linearly correlated with the decrease in the oxygen extraction fraction in the same region; that is, it was correlated with the occurrence of perfusion in excess of metabolic demand. The overabundant local perfusion could play a role in the decreased H+ content.

Acid-Base Equilibrium↗

[55Co]- and [64Cu]DTPA: new radiopharmaceuticals for quantitative tomocisternography.

The diethylenetriaminepentaacetic acid (DTPA) complexes of the convenient half-life positron emitters 55Co and 64Cu have been prepared for quantitation of cerebrospinal fluid (CSF) kinetics in different areas of the brain using positron emission tomography. The radionuclides are prepared by proton bombardment of natural nickel (58Ni(p, alpha)55 Co and 64Ni (p,n)64Cu reactions). The chemical separation of the radionuclides from the target is described, and the production yields, radionuclidic purities and specific activities are given.

Brain Diseases↗

Comparison of 11C-L-methionine uptake by the parotid gland and pancreas in chronic pancreatitis studied by positron emission tomography.

L-methionine uptake by the parotid gland and pancreas has been compared in 27 patients using a non-invasive methodology. L-methionine was labelled with 11C, a positron emitter with a short half life produced in a cyclotron. 11C-L-methionine concentration was measured in the parotid glands and in the pancreas by external detection using a positron emission tomographic system. 11C-L-methionine uptake by the parotid glands was 4.3 X 10(-3) +/- 1.9 X 10(-3)% of the injected dose per millilitre of tissue (mean +/- SD) in a group of 11 normal non-alcoholic subjects. The uptake was 3.6 +/- 1.3 (X10(-3) in a group of nine alcoholic subjects without pancreatic disorder and it was 4.9 +/- 1.5 (X10(-3) in a third group of seven patients with chronic pancreatitis. These values did not significantly differ. In contrast median pancreatic uptake of 11C-L-methionine was nil in chronic pancreatitis and was lower than that seen in normal subjects (15.3 X 10(-3)% ml, p less than 0.001) and in alcoholic subjects (11.5 X 10(-3)% ml, p less than 0.002). Thus neutral long chain amino acid transport in the parotid gland appears to be independent of that in the exocrine pancreas in chronic pancreatitis. This absence of relationship between the parotid gland and the pancreas in pancreatic disease is in contradiction with the demonstration made in animals of an interaction between these two glands. These results, however, are in agreement with the conclusions drawn from the data collected from the saliva test used by several authors.

Adult↗

Influence of hypertonic bolus injection on capillary transport of water, urea and albumin in dog lung.

The influence of hypertonic bolus on dog lung capillary permeability was determine by the in vivo osmotic transient method associated with the multiple indicator dilution method. Three instantaneous injections were made (into the pulmonary artery) at 20 min intervals. The first was an isotonic bolus of 14C-Urea and 125I-Albumin tracers. The second was a hypertonic bolus of urea also with 14C-Urea and 125I-Albumin tracers. The third was identical to the first. Simultaneously, blood samples were withdrawn from the aorta and radioactive concentration of the tracers was measured. No difference between extraction of the test tracer (14C-Urea) was found between any of the three injections (=E1 = 0.108; -E2 = 0.096; -E3 = 0.096). Comparison of the permeability surface-area product values confirmed this absence of modification. It was concluded that the hypertonic bolus did not change capillary permeability to a small hydrophilic molecule and that the solvent drag induced by hyperosmotic transient was negligible.

Albumins↗

Synthesis and in vivo characteristics of [2-11 C]5,5-dimethyloxazolidine-2,4-dione (DMO).

No-carrier-added [2-11 C]5,5-dimethyloxazolidine-2,4-dione (DMO) has been prepared rapidly and in good radiochemical yield. The synthesis involves in situ conversion of phosgene to diethyl carbonate which reacts with 2-hydroxy-2-methylpropionamide to yield labeled DMO. HPLC purification provided up to 1.85 GBq (50 mCi) of pure [11C]-DMO for injection. The product's in vivo distribution was examined in mice and rabbits. The results are encouraging for further application to in vivo measurement of intracellular pH using positron tomography.

Animals↗

The role of positron emission tomography in the detection of pancreatic disease.

Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of 11C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D). of injected 11C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic 11C concentration was identical in the four groups of patients. Pancreatic uptake of 11C-L-methionine was significantly lower in patients with chronic pancreatitis (n = 13) and pancreatic carcinoma (n = 10) (p less than 0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both.

Carbon Radioisotopes↗