Distribution of intranasal C-zolmitriptan assessed by positron emission tomography.

Nine healthy volunteers aged 18-28 years were recruited into this open, single-centre, two-phase trial. In phase 1, two volunteers received a single dose of 11C-zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron emission tomography (PET) scanning to determine the most appropriate times for scanning in phase 2.

Pheochromocytomas: detection with 11C hydroxyephedrine PET.

Purpose: To evaluate the accuracy of carbon 11 (11C) hydroxyephedrine (HED) positron emission tomography (PET) in the detection of pheochromocytomas.

Materials And Methods: Nineteen patients (12 women, seven men; mean age, 53 years) suspected of having pheochromocytoma were evaluated. Patients had enlarged adrenal glands at computed tomography and either increased urinary catecholamine levels (n = 18) or normal biochemistry (n = 1).

The role of PET in localization of neuroendocrine and adrenocortical tumors.

Positron emission tomography (PET) supplies a range of labeled compounds to be used for the characterization of tumor biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow up, and clinical research. The first routinely used PET tracer in oncology, (18)F-labeled deoxyglucose (FDG), was successfully used for diagnosis of cancer, reflecting increased expression of glucose transporter in cancerous tissue.

Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients.

Using R-beta-[1-(11)C]hydroxybutyrate and positron emission tomography, we studied the effect of acute hyperketonemia (range 0.7-1.7 micromol/ml) on cerebral ketone body utilization in six nondiabetic subjects and six insulin-dependent diabetes mellitus (IDDM) patients with average metabolic control (HbA(1c) = 8.

Positron emission tomography and brain monoamine neurotransmission -- entries for study of drug interactions.

Monoamine neurotransmission is a complicated process with interactions between individual neurotransmitter pathways, multiple receptors with different responses and a variety of feedback loops regulating neurotransmitter synthesis, release, reuptake and effect on receptors. The system is further affected by a range of enzymes with co-factors controlling synthesis and degradation of monoamines. Positron emission tomography (PET) has evolved to a very versatile tool for the in vivo imaging and characterisation of physiology and biochemistry.

[(11)C] Carbon monoxide in selenium-mediated synthesis of (11)C-carbamoyl compounds.

Using either amines, amino alcohols, or alcohols in selenium-mediated synthesis with [(11)C]carbon monoxide, 3 ureas, 6 carbamates, and 1 carbonate were labeled. Tetrabutylammonium fluoride ((TBA)F) was discovered to form a soluble and reactive complex with selenium and drastically increase the radiochemical yields. Of the selected carbamoyl compounds, one was a receptor ligand, one was an enzyme inhibitor, and one was a muscular relaxant pharmaceutical.

Interaction of a muscarinic cholinergic agonist on acetylcholine and dopamine receptors in the monkey brain studied with positron emission tomography.

The effects on the binding to cholinergic and dopaminergic receptors in the brain during continuous intravenous infusion of the muscarinic cholinergic receptor agonist milameline (CI-979) were studied in the rhesus monkey by means of positron emission tomography. Binding to milameline cholinergic receptors was quantified using the muscarinic receptor antagonist [(11)C]-N-methyl-4-piperidinylbenzilate ([(11)C]NMP), and the effects on nicotine receptor binding were measured with (S)-[(11)C-methyl]nicotine. Changes in the binding of the D(2) dopamine receptor antagonist [(11)C]raclopride were measured as well.

The synthesis of [26,27-11C]dihydroxyvitamin D(3), a tracer for positron emission tomography (PET).

1Alpha,25-dihydroxyvitamin D(3), an endogenous ligand with the highest affinity for the vitamin D receptor (VDR), was labeled with 11C for use in biological experiments. The radionuclide was incorporated via the reaction of [11C]methyllithium on a methyl ketone precursor in tetrahydrofuran at -10 degrees C. Deprotection of the labeled intermediate yielded 2.

PET with 11C-deuterium-deprenyl and 18F-FDG in focal epilepsy.

Objectives: This study compares positron emission tomography (PET) using 11C-deuterium-deprenyl (DED) with PET using 18F-fluorodeoxyglucose(18F-FDG) for examining epileptogenic regions in patients with focal epilepsy.

Material And Methods: Twenty-three patients undergoing evaluation for epilepsy surgery were subjected to PET with DED. Fourteen patients had mesial temporal lobe epilepsy (TLE) and 9 patients had seizures of neocortical origin.

Use of positron emission tomography in analysing receptor function in vivo.

The non-invasive radiotracer technique positron emission tomography (PET) may provide valuable information in the toxicokinetic-toxicodynamic evaluation of endogenous or toxic environmental compounds. Assessment of mechanism of action of toxins is often difficult to validate. In this respect, PET may offer advantages since it can quantify not only the distribution and kinetics of the radiolabelled toxin in the body, but also the altered rates of physiological or biochemical processes induced by the toxin.

6. 18F-FDG Whole Body Positron Emission Tomography (PET) in the Detection of Unknown Primary Tumors.

Purpose: To evaluate the utility of FDG-PET in detecting primary tumors in patients with metastatic disease from unknown primary tumors.Methods: 12 patients with metastases from unknown origin after unsuccessful conventional diagnostic procedures were studied. 5 had lymph node metastases (2 axillary, 2 cervical, 1 mediastinal), 3 multiple metastases, 1 in the lung, 1 in the cava vein, 1 in the brain and 1 in adrenal glands.

Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies.

Positron emission tomography (PET) performed with various radiolabelled compounds facilitates the study of tumor biochemistry. If the tumor uptake of an administered tracer is greater than that of surrounding normal tissue, it is also possible to localize the tumor. In initial studies, 18F-labeled deoxyglucose (FDG) was attempted to visualize the tumors, since this tracer had been successfully used in oncology, reflecting increased glucose metabolism in cancerous tissue.

Distribution of (76)Br-labeled antisense oligonucleotides of different length determined ex vivo in rats.

Oligonucleotides may hybridize with high selectivity to an RNA sequence and can be used for the monitoring of gene expression or for its inhibition in experimental or therapeutic purposes. As part of the development of positron emission tomography (PET) methods, different lengths (30, 20, 12 and 6 mer) of antisense phosphorothioate oligonucleotides complementary to rat chromogranin A were labeled with [(76)Br] using a prosthetic group. The (76)Br-oligonucleotides were injected into rat's tail vein (1-2 MBq/rat), and the radioactivity distribution was analyzed after 20 h using whole body autoradiography or by measurement of organ radioactivity concentration.

Brain uptake and receptor binding of two [11C]labelled selective high affinity NK1-antagonists, GR203040 and GR205171--PET studies in rhesus monkey.

Two high affinity and selective NK1-receptor antagonists, GR203040 and GR205171, were labelled with 11C and used in a series of experiments in rhesus monkeys. The purpose of these studies was to evaluate the brain uptake pattern and to explore the potential use of these compounds as PET ligands to characterise NK1-receptor binding. Seventeen studies were carried out with [11C]GR205171 and five experiments with [11C]GR203040, including baseline studies and studies performed after a 5 min infusion of cold compound at doses between 0.

Elimination of nonspecific radioactivity from [76Br]bromide in PET study with [76Br]bromodeoxyuridine.

[76Br]Bromodeoxyuridine ([76Br]BrdU) might allow a determination of proliferation in vivo using positron emission tomography (PET), but only with consideration of organ nonspecific radioactivity constituted by [76Br]bromide. A first study assessed the potential of diuretics to eliminate [76Br]bromide. [76Br]Bromide was injected in the vein of rats and different diuretic combinations were given.

A mechanism behind the antitumour effect of 6-diazo-5-oxo-L-norleucine (DON): disruption of mitochondria.

6-diazo-5-oxo-L-norleucine (DON) exerts a growth inhibitory effect selectively on the neuroendocrine tumour cell line BON and is proposed as an antitumour drug. The mechanism behind this has not yet been clarified. In the present study, transmission electron microscopy was used for the assessment of changes in cellular organelles.

Compounds labelled with short-lived beta(+)-emitting radionuclides and some applications in life sciences. The importance of time as a parameter.

Some examples of recent development of the synthesis of compounds labelled with short-lived beta(+)-emitting radionuclides will be discussed with an emphasis on the importance of time in selecting a synthetic strategy. Furthermore the use of such labelled compounds to monitor certain processes in areas within the field of analytical chemistry and in various applications in drug development will be presented.

Deposition and disposition of [11C]zanamivir following administration as an intranasal spray. Evaluation with positron emission tomography.

Objective: This study used positron emission tomography (PET) to investigate the deposition and disposition of zanamivir administered as a nasal spray.

Design: This was an open-label single-dose study in healthy volunteers.

Study Participants: Six healthy male volunteers, aged 19 to 33 years (mean age 25 years) with a bodyweight of 65 to 94 kg (mean bodyweight 76 kg), took part in the study.

A multivariate approach to registration of dissimilar tomographic images.

We devised a method to allow for retrospective registration of tomographic images with very different information content, the main emphasis being on sets of positron emission tomography images obtained with different tracers. A multivariate cost-function based on information theory was used as an index of "goodness-of-alignment". The cost-function makes no assumptions regarding the form of the relationship between the two image sets, and is hence very general.

Effect of apomorphine infusion on dopamine synthesis rate relates to dopaminergic tone.

The effects of apomorphine on the striatal L-[11C]DOPA influx rate was examined in anaesthetized Rhesus monkeys using positron emission tomography (PET). In comparison with baseline conditions, the addition of a continuous infusion of apomorphine produced decreases in the striatal L-[11C]DOPA influx rate in all the monkeys examined. The effect of apomorphine infusion also showed a dose-dependent trend.