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Results for “Carbon Radioisotopes”

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At least 19 recordsLinked to original sources
PubMed2005

A positron emission tomography radioligand for the in vivo labeling of metabotropic glutamate 1 receptor: (3-ethyl-2-[11C]methyl-6-quinolinyl)(cis- 4-methoxycyclohexyl)methanone.

A selective metabotropic glutamate 1 receptor (mGlu1) antagonist was labeled with the positron-emitting radioisotope carbon-11 and evaluated in ex vivo biodistribution studies and micro-positron emission tomography (micro-PET) imaging experiments in rats. Results from animal experiments demonstrate that the radioligand [11C]2 is the first PET tracer capable of labeling the rat mGlu1 receptor in vivo.

Animals↗
PubMed2005

Determination of trichloroacetic acid in environmental studies using carbon 14 and chlorine 36.

Radioisotopes carbon 14 and chlorine 36 were used to elucidate the environmental role of trichloroacetic acid (TCA) formerly taken to be a herbicide and a secondary air pollutant with phytotoxic effects. However, use of 14C-labeling posed again known analytical problems, especially in TCA extraction from the sample matrix. Therefore--after evaluation of available methods--a new procedure using decarboxylation of [1,2-14C]TCA combined with extraction of the resultant 14C-chloroform with a non-polar solvent and its subsequent radiometric measurement was developed. The method solves previous difficulties and permits an easy determination of amounts between 0.4 and 20 kBq (10 - 500 ng g(-1)) of carrier-less [1,2-14C]TCA in samples from environmental investigations. The procedure is, however, not suitable for direct [36Cl]TCA determination in chlorination studies with 36Cl. Because TCA might be microbially degraded in soil during extraction and sample storage and its extraction from soil or needles is never complete, the decarboxylation method--i.e. 2 h TCA decomposition to chloroform and CO2 in aqueous solution or suspension in closed vial at 90 degrees C and pH 4.6 with subsequent CHCl3 extraction-is recommended here, estimated V < 7%. Moreover, the influence of pH and temperature on the decarboxylation of TCA in aqueous solution was studied in a broad range and its environmental relevance is shown in the case of TCA decarboxylation in spruce needles which takes place also at ambient temperatures and might amount more than 10-20% after a growing season. A study of TCA distribution in spruce needles after below-ground uptake shows the highest uptake rate into current needles which have, however, a lower TCA content than older needle-year classes, TCA biodegradation in forest soil leads predominatingly to CO2.

Carbon Radioisotopes↗
PubMedDate not supplied

Radiolabeled ligands for imaging the muscarinic-cholinergic receptors of the heart and brain.

Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on IQNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the "partial" subtype selective IQNP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

Animals↗
PubMed2001

Comparative biodistribution and metabolism of carbon-11-labeled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide and DNA-intercalating analogues.

The tricyclic carboxamide N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is a DNA-intercalating agent capable of inhibiting both topoisomerases I and II and is currently in Phase II clinical trial. Many related analogues have been developed, but despite their potent in vitro cytotoxicities, they exhibit poor extravascular distribution. As part of an ongoing drug development program to obtain related "minimal intercalators" with lower DNA association constants, we have compared the biodistribution and metabolite profiles of the prototype compound, DACA, with three analogues to aid rational drug selection. All of these compounds share a common structural feature, N-dimethyl side chain, which was radiolabeled with the positron-emitting radioisotope, carbon-11. This strategy was selected because it allows promising candidates emerging from preclinical studies in animals to be evaluated rapidly in humans using positron emission tomography (PET). The acridine DACA, the phenazine SN 23490, the pyridoquinoline SN 23719, and the dibenzodioxin SN 23935 were found to be cytotoxic in in vitro assays with an IC50 of 1.4-1.8 microM, 0.4-0.6 microM, 1.3-1.6 microM, and 24-36 microM, respectively, in HT29, U87MG, and A375M cell lines. Ex vivo biodistribution studies with carbon-11 radiolabeled compounds in mice bearing human tumor xenografts showed rapid clearance of 11C-radioactivity (parent drug and metabolites) from blood and the major organs. Rapid hepatobiliary clearance and renal excretion were also observed. There was low [<5% of injected dose/gram (%ID/g)] and variable uptake of 11C-radioactivity in three tumor types for all of the compounds. Tumor (U87MG) to blood 11C-radioactivity for [11C]DACA, [11C](9-methoxyphenazine-1-carboxamide (SN 23490), [11C]2-(4-pyridyl)quinoline-8-carboxamide (SN 23719), and [11C]dibenzo[1,4]dioxin-1-carboxamide (SN 23935) at 30 min were 2.9 +/- 1.1, 2.3 +/- 0.6, 2.6 +/- 0.6, and 0.7 +/- 0.2, respectively. For SN 23719, the distribution of 11C-radioactivity in normal tissues and tumors determined ex vivo was in broad agreement with that determined in vivo by whole body PET scanning. [11C]DACA was rapidly and extensively metabolized to several plasma metabolites and a major tumor metabolite. In contrast, [11C]SN 23935, [11C]SN 23490, and [11C]SN 23719 showed less extensive metabolism. In the tumor samples, the parent [11C]DACA and [11C]SN 23935 represented between 0.3 and 1.5%ID/g, whereas [11C]SN 23490 and [11C]SN 23719 represented between 1.5 and 2.8%ID/g. In conclusion, by using a strategy with 11C-labeling, we have determined the tissue distribution and metabolic stability of novel tricyclic carboxamides with the view of selecting analogues with potentially better in vivo activity against solid tumors. SN 23490 and SN 23719 had more favorable distribution and metabolic stability compared with DACA and SN 23935 and may warrant further development. The radiolabeling strategy used allows ex vivo and in vivo evaluation of promising anticancer agents in animals and offers the potential of rapid translation to studies in humans using PET.

Acridines↗
PubMed1982

Short-lived radionuclides in nutritional physiology. A model study with L-[Me-11C]methionine in the pig.

1. A "new" carbon radioisotope, 11C, for use in nutritional studies is presented. It has a 20 min half-life, and decays by positron emission giving annihilation photons of 511 keV energy (Wolf & Redvanly, 1977). Thus repeated studies can be made with short time intervals and the distribution of radioactivity in the experimental animal can be detected externally. 2. 11C was produced with a tandem Van de Graaff accelerator and L-[me-11C]methionine was synthesized and used in model experiments in the pig. The tracer was administered intravenously through a catheter in the jugular vein of pigs weighing between 40 and 100 kg. In a series of experiments, one pig received a low-methionine diet supplemented with DL-methionine to give three different levels of methionine intake. 3. The radioactivity distribution between liver and muscle was measured as a function of time by external detector for 2-3 h after administration. Blood and exhaled CO2 were sampled and measured for radioactivity. 4. The results indicate that 11C is a useful radionuclide in nutritional studies in intact large domestic animals.U

Animal Nutritional Physiological Phenomena↗
PubMed1975

In vivo myocardial cell pH in the dog. Response to ischemia and infusion of alkali.

Myocardial cell pH has been measured with 5,5-dimethyl-2,4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular, and water indicators were made into the anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady-state distribution of DMO between cells and plasma was calculated from the indicator mean transit times, and the plasma pH. Myocardial cell pH was determined from the distribution value and plasma pH. Normal myocardial cell pH averaged 6.94. Changes in myocardial cell pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a coronary artery balloon resulted in progressive decreases in cellular pH to average values of 6.83 within the initial 15 min and to 6.59 within the interval between 20 and 70 min. Infusions of Na2CO3 tended to diminish intracellular acidosis although these infusions had little effect on the difference in pH between the myocardial cell and extracellular fluid.

Acid-Base Equilibrium↗
PubMed2005

Depolarization ratio and correlation between the relative intensity data and the abundance ratio of various isotopes of liquid carbon tetrachloride at room temperature.

The room temperature Stokes and anti-Stokes Raman spectra of liquid CCl(4) have been recorded. The intensity ratios of anti-Stokes to Stokes Raman bands as a function of Raman shift are obtained in agreement with polarizability theory. The depolarization ratio rho (nu) as a function of Raman shift is obtained also in agreement with automatically scanned depolarization ratio rho (nu). Ratio of the intensity of the isotopic nu(1) bands indicates small deviation from the theoretical relative abundance of CCl(4) isotopes. The intensity ratio of the [nu(3)-nu(4), (nu(1)+nu(4))-nu(4)] and nu(1) bands is obtained. The consequences of the presence of different isotopes of CCl(4) on the depolarization ratio of its vibrational bands are discussed. The effects of impurities in liquid CCl(4) on depolarization ratio of the nu(1) band are estimated.

Carbon Isotopes↗
PubMed2004

14C and delta13C characteristics of organic matter and carbonate in saltmarsh sediments from south west Scotland.

The distribution of contaminant radionuclides from the Sellafield nuclear fuel reprocessing plant was used to establish chronologies for three saltmarsh sediment cores from south west Scotland. delta(13)C and (14)C analyses indicated that the cores provided a useful archive record of variations in input of organic matter and carbonate. The results imply that prior to major releases of contaminant (14)C from Sellafield, the (14)C specific activity of organic matter in Irish Sea offshore sediments was about 24 Bq kg(-1) C, while that of the carbonate component was below the limit of detection. These results provide baseline data for modelling the uptake of contaminant (14)C by the Irish Sea sediment system. The study confirmed that small(13)C analyses provide a sensitive means of apportioning the origin of saltmarsh organic matter between C(3) terrigenous plants, C(4) terrigenous plants and suspended particulate marine organic matter. For the <2 mm fraction of sediment, a clear pattern of decreasing marine organic input was observed in response to increasing elevation of the marsh surface as a result of sediment accumulation. Bulk sediment, including detrital vegetation, had a dominant input from terrigenous plants. The combined use of delta(13)C and (14)C data revealed that organic matter in the marine organic component of the <2 mm fraction of contemporary surface sediments of the saltmarshes is dominated by recycled old organic material.

Carbon Radioisotopes↗