Amsterdam, Netherlands
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Janssen B.,VU University Amsterdam | Vugts D.J.,VU University Amsterdam | Funke U.,VU University Amsterdam | Spaans A.,VU University Amsterdam | And 6 more authors.
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2014

Neuroinflammation, in particular activation of microglia, is thought to play an important role in the progression of neurodegenerative diseases. In activated microglia, the purinergic P2X7 receptor is upregulated. A-740003, a highly affine and selective P2X7 receptor antagonist, is a promising candidate for the development of a radiotracer for imaging of neuroinflammation by positron emission tomography. For this purpose, [ 11C]A-740003 was synthesised and evaluated in vivo with respect to both tracer metabolism and biodistribution. In plasma, a moderate metabolic rate was seen. In healthy rat brain, only marginal uptake of [11C]A- 740003 was observed and, therefore, metabolites in brain could not be determined. Whether the minimal brain uptake is due to the low expression levels of the P2X7 receptor in healthy brain or to limited transport across the blood-brain barrier has yet to be elucidated. For the development of a radiotracer for imaging of neuroinflammation by positron emission tomography, [11C]A-740003 was synthesised and evaluated in vivo in healthy male Wistar rats with respect to both tracer metabolism and biodistribution. Copyright © 2014 John Wiley & Sons, Ltd.


Funke U.,BV Cyclotron VU | Funke U.,VU University Amsterdam | Vugts D.J.,VU University Amsterdam | Janssen B.,VU University Amsterdam | And 6 more authors.
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2013

The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography. This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, we could examine the H1R expression in the human brain in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1R occupancy. The H3R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3R positron emission tomography imaging studies in humans have been reported. The H4R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4R-specific 11C-labeled ligands have been synthesized, and the imaging of the H4R in vivo is in the early stage. Copyright © 2013 John Wiley & Sons, Ltd.


Janssen B.,VU University Amsterdam | Vugts D.J.,VU University Amsterdam | Funke U.,VU University Amsterdam | Funke U.,BV Cyclotron VU | And 6 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2016

Neuroinflammation is thought to play a pivotal role in many diseases affecting the brain, including Alzheimer's disease, multiple sclerosis and stroke. Neuroinflammation is characterised predominantly by microglial activation, which can be visualised using positron emission tomography (PET). Traditionally, translocator protein 18 kDa (TSPO) is the target for imaging of neuroinflammation using PET. In this review, recent preclinical and clinical research using PET in Alzheimer's disease, multiple sclerosis and stroke is summarised. In addition, new molecular targets for imaging of neuroinflammation, such as monoamine oxidases, adenosine receptors and cannabinoid receptor type 2, are discussed. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. © 2015 Elsevier B.V.


Hofman M.B.M.,VU University Amsterdam | Hofman M.B.M.,BV Cyclotron VU | Kuijer J.P.A.,VU University Amsterdam | Kuijer J.P.A.,BV Cyclotron VU | And 6 more authors.
Medical Physics | Year: 2013

Purpose: With the introduction of hybrid PET/MRI systems, it has become more likely that the cyclotron and MRI systems will be located close to each other. This study considered the interference between a cyclotron and a superconducting MRI system. Methods: Interactions between cyclotrons and MRIs are theoretically considered. The main interference is expected to be the perturbation of the magnetic field in the MRI due to switching on or off the magnetic field of the cyclotron. MR imaging is distorted by a dynamic spatial gradient of an external inplane magnetic field larger than 0.5-0.04 μT/m, depending on the specific MR application. From the design of a cyclotron, it is expected that the magnetic fringe field at large distances behaves as a magnetic dipolar field. This allows estimation of the full dipolar field and its spatial gradients from a single measurement. Around an 18 MeV cyclotron (Cyclone, IBA), magnetic field measurements were performed on 5 locations and compared with calculations based upon a dipolar field model. Results: At the measurement locations the estimated and measured values of the magnetic field component and its spatial gradients of the inplane component were compared, and found to agree within a factor 1.1 for the magnetic field and within a factor of 1.5 for the spatial gradients of the field. In the specific case of the 18 MeV cyclotron with a vertical magnetic field and a 3T superconducting whole body MR system, a minimum distance of 20 m has to be considered to prevent interference. Conclusions: This study showed that a dipole model is sufficiently accurate to predict the interference of a cyclotron on a MRI scanner, for site planning purposes. The cyclotron and a whole body MRI system considered in this study need to be placed more than 20 m apart, or magnetic shielding should be utilized. © 2013 American Association of Physicists in Medicine.


PubMed | VU University Amsterdam and BV Cyclotron VU
Type: Journal Article | Journal: Biochimica et biophysica acta | Year: 2016

Neuroinflammation is thought to play a pivotal role in many diseases affecting the brain, including Alzheimers disease, multiple sclerosis and stroke. Neuroinflammation is characterised predominantly by microglial activation, which can be visualised using positron emission tomography (PET). Traditionally, translocator protein 18kDa (TSPO) is the target for imaging of neuroinflammation using PET. In this review, recent preclinical and clinical research using PET in Alzheimers disease, multiple sclerosis and stroke is summarised. In addition, new molecular targets for imaging of neuroinflammation, such as monoamine oxidases, adenosine receptors and cannabinoid receptor type 2, are discussed. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.

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