positron-emission-tomography-using-64-copper-as-tracer-for-study

Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders

Copper is an essential trace element, functioning in catalysis and signaling in biological systems. Radiolabeled copper has been used for decades in ...

Aarhus University Hospital

Positron emission tomography (PET) imaging of the norepinephrine transporter (NET) is still hindered by the availability of useful PET imaging probes. The present study describes the radiosynthesis and pre-clinical evaluation of a new compound, exo-3-(6-methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine.

[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter.

Brain cholinergic function has been previously studied with PET but little effort has been devoted to imaging peripheral organs. Many disorders, including diabetes and Parkinson disease, are associated with autonomic dysfunction including parasympathetic denervation. Nonneuronal cholinergic signaling is also involved in immune responses to infections and in cancer pathogenesis. 5-(11)C-methoxy-donepezil, a noncompetitive acetylcholinesterase ligand, was previously validated for imaging cerebral levels of acetylcholinesterase. In the present study, we explored the utility of (11)C-donepezil for imaging acetylcholinesterase densities in peripheral organs, including the salivary glands, heart, stomach, intestine, pancreas, liver, and spleen.

In vivo imaging of human acetylcholinesterase density in peripheral organs using 11C-donepezil: dosimetry, biodistribution, and kinetic analyses.

γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system acting mainly through GABAreceptors. In the presence of high levels of GABA, an allosteric shift in the GABAreceptors can change the affinity of benzodiazepine (BZD) ligands. Valproic acid (VPA) is an anticonvulsant that enhances the level of endogenous GABA in the brain. The BZD ligand, Ro15-4513 has a high affinity for GABAreceptors containing the αsubunit and can be used to investigate the GABA shift in the brains of living rats after VPA exposure. Seven Wistar rats were scanned using a Mediso NanoScan PET/MRI. A baseline 90-min dynamic [C]Ro15-4513 PET scan was acquired prior to an intravenous injection of 50 mg/kg VPA, and was followed by a second [C]Ro15-4513 PET scan. Standardized uptake values were obtained for regions of high GABA binding, including the hippocampus and amygdala, and low GABA binding such as the cerebellum. We showed a significant increase in [C]Ro15-4513 uptake in hippocampus and amygdala, but no significant differences in cerebellar uptake, after acute VPA exposure. In contrast to several in vitro studies, we demonstrated a positive allosteric change in the GABAreceptors after pharmacologically enhanced GABA levels resulting in enhanced Ro15-4513 uptake. Knowledge of how subtypes of the GABAreceptors react will provide us with information useful to fine-tune pharmacological interventions and design receptor subtype specific drugs.

Acute in vivo effect of valproic acid on the GABAergic system in rat brain: A [C]Ro15-4513 microPET study.

Copper is essential for enzymatic processes throughout the body. [Cu]copper (Cu) positron emission tomography (PET) has been investigated as a diagnostic tool for certain malignancies, but has not yet been used to study copper homeostasis in humans. In this study, we determined the hepatic removal kinetics, biodistribution and radiation dosimetry of Cu in healthy humans by both intravenous and oral administration.

Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by [Cu]copper PET/CT.

Wilson's disease (WD) is a genetic disease with systemic accumulation of copper that leads to symptoms from the liver and brain. However, the underlying defects in copper transport kinetics are only partly understood. We sought to quantify hepatic copper turnover in patients with WD compared with heterozygote and control subjects using PET with copper-64 ( Cu) as a tracer. Furthermore, we assessed the diagnostic potential of the method.

Karina Vase

Department of Nuclear Medicine & PET-Center

Aarhus University Hospital

Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders

Karina Vase

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Nuclear Medicine & PET-Center

Aarhus University Hospital

Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders

Department of Nuclear Medicine & PET-Center