Evidence for a relationship between mitochondrial Complex I activity and mitochondrial aldehyde dehydrogenase during nitroglycerin tolerance: effects of mitochondrial antioxidants.

The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GTN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GTN tolerance (in rat and human vessels) produced a decrease in mitochondrial O(2) consumption.

Positron emission tomographic imaging of the cannabinoid type 1 receptor system with [¹¹C]OMAR ([¹¹C]JHU75528): improvements in image quantification using wild-type and knockout mice.

In this study, we assessed the feasibility of using positron emission tomography (PET) and the tracer [¹¹C]OMAR ([¹¹C]JHU75528), an analogue of rimonabant, to study the brain cannabinoid type 1 (CB1) receptor system. Wild-type (WT) and CB1 knockout (KO) animals were imaged at baseline and after pretreatment with blocking doses of rimonabant. Brain uptake in WT animals was higher (50%) than in KO animals in baseline conditions.

Oxidative stress and mitochondrial dysfunction in type 2 diabetes.

Diabetes is a chronic disease and as a consequence of the overproduction of reactive oxygen species (ROS), is related with oxidative stress. There are different sources of ROS, of which mitochondria is the main one. Oxidative stress seems to play an important role in mitochondria- mediated disease processes, though the exact molecular mechanisms responsible remain elusive.

[(11)C]-DASB microPET imaging in the aged rat: frontal and meso-thalamic increases in serotonin transporter binding.

Whereas molecular imaging studies in the aging human brain have predominantly demonstrated reductions in serotonin transporter (5-HTT) availability, the majority of the rodent studies, using autoradiographic methods, report increases in neural 5-HTT levels with age. To our knowledge, however, no previous rodent studies have assessed this topic in vivo, and therefore it remains unclear whether this discrepancy arises from methodological or inter-species differences. We performed an [(11)C]-DASB microPET study to evaluate the effects of aging on 5-HTT availability in the rat brain.

Mitochondrial antioxidants alleviate oxidative and nitrosative stress in a cellular model of sepsis.

Purpose: Mitochondrial dysfunction plays a key role in sepsis.

Methods: We used a sepsis model of human endothelial cells (HUVEC) to study mitochondrial function during normoxic (21% O(2)) and hypoxic (1% O(2)) conditions.

Results: When stimulated with a LPS cocktail, HUVEC displayed an increase of nitric oxide (NO) in normoxic and hipoxic conditions, being higher at 21% O(2).

Translational characterization of [11C]GSK931145, a PET ligand for the glycine transporter type 1.

The current interest in developing Glycine transporter Type 1 (GlyT-1) inhibitors, for diseases such as schizophrenia, has led to the demand for a GlyT-1 PET molecular imaging tool to aid drug development and dose selection. We report on [(11) C]GSK931145 as a novel GlyT-1 imaging probe in primate and man. Primate PET studies were performed to determine the level of specific binding following homologous competition with GSK931145 and the plasma-occupancy relationship of the GlyT-1 inhibitor GSK1018921.

Biodistribution of amino-functionalized diamond nanoparticles. In vivo studies based on 18F radionuclide emission.

Nanoparticles have been proposed for several biomedical applications; however, in vivo biodistribution studies to confirm their potential are scarce. Nanodiamonds are carbon nanoparticles that have been recently proposed as a promising biomaterial. In this study, we labeled nanodiamonds with (18)F to study their in vivo biodistribution by positron emission tomography.

In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain.

The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats.

Biodistribution and radiation dosimetry of the glycine transporter-1 ligand 11C-GSK931145 determined from primate and human whole-body PET.

Purpose: (11)C-GSK931145 is a novel radioligand suitable for imaging the glycine transporter 1 (GlyT-1) in brain. In the present study, human dosimetry is estimated from baboon and human biodistribution data.

Procedures: Three baboons and eight healthy human volunteers underwent whole-body positron emission tomography (PET) scans.

Simultaneous dual-tracer PET imaging of the rat brain and its application in the study of cerebral ischemia.

Purpose: This study evaluates the performance of simultaneous dual-tracer technique (SDTT) in static positron emission tomography (PET) studies using 2-deoxy-2-[¹⁸F]fluoro-D-glucose and [¹³N]ammonium as radiotracers.

Procedures: The effects of applying SDTT either to the reconstructed image or directly to the sinogram, different rebinning algorithms, total acquisition time, and frame duration were investigated; first, using a specific phantom and later using an in vivo application of the study of cerebral ischemia.

Results: The best results were obtained using the image method with single-slice rebinning and a total acquisition time of at least 20 min.

Imaging cortical dopamine D1 receptors using [11C]NNC112 and ketanserin blockade of the 5-HT 2A receptors.

[(11)C]NNC112 (8-chloro-7-hydroxy-3-methyl-5-(7-benzofuranyl)-2,3,4,5-tetrahydro-IH-3-benzazepine), a selective positron-emission tomography (PET) ligand for the D(1) receptor (R) over the 5-HT(2A) R in vitro, has shown lower selectivity in vivo, hampering measurement of D(1) R in the cortex. [(11)C]NNC112 PET and intravenous (i.v) ketanserin challenge were used to (1) confirm the previous findings of [(11)C]NNC112 in vivo D(1) R selectivity, and (2) develop a feasible methodology for imaging cortical D(1) R without contamination by 5-HT(2A) R.