[18F]SV2A – early diagnosis

In a transgenic mouse model, overexpressing human α–syn under the mThy1 promotor (Parkinson mouse model), researchers have proved that the new SV2A-radioligand developed at CRC is a valid biomarker to study the loss of synaptic terminals appearing before the occurrence of behavioral disturbances.

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[18F]FMT – evaluation of dopaminergic dysfunction

Researchers at CRC have evaluated the feasibility of in vivo PET study using 6-[18F]fluoro-m-tyrosine (6-[18F]FMT) on lesioned rats with 6-hydroxydopamine (6-OHDA), a rat model of Parkinson’s disease (PD).

The (6-[18F]FMT) is an effective PET tracer to evaluate DA terminals integrity and L-aromatic amino acid decarboxylase (AAAD) metabolic pathway.

Using this PET tracer, they were able to quantify loss of DA presynaptic function in unilaterally 6-OHDA lesioned rats.

Researchers are currently investigating this tracer in a longitudinal way to monitor the progression of dopaminergic dysfunction in more moderate and gradual preclinical PD models.

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MPTP-treated mice

Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibit a large decrement in the neostriatal content of dopamine and its metabolites, a marked reduction in the capacity of neostriatal synaptosomal preparations to accumulate [3H]dopamine, a large decrease in neostriatal tyrosine hydroxylase activity, a marked loss of nerve cells in the zona compacta of the substantia nigra and pronounced behavioral deficits. These biochemical, pathological and behavioral deficits are similarly observed in MPTP-treated primates and in humans with idiopathic Parkinsonism.

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Thy1-aSyn transgenic mice

This mouse model over-expresses full-length, human, wild-type alpha-synuclein under the Thy-1 promoter.

It has been shown to reproduce many features of sporadic Parkinson Disease (PD), including progressive changes in dopamine release and striatal content, alpha-synuclein pathology, deficits in motor and non-motor functions that are affected in pre-manifest and manifest phases of PD, inflammation and biochemical and molecular changes similar to those observed in PD.

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Electrophysiology

electrophysio_in vivo$Electrophysiology aims at a better understanding of the role of various types of ionic channels in the modulation of neuronal activity. More particularly, it helps to:

  • Evaluate the role of various ionic channels (SK K+ channels, M type K+ channels, voltage gated Na+, K+ and Ca²+ channels) in the control of the excitability of mesencephalic monoaminergic neurons;
  • Better understand the biophysical properties of the proteins making up these channels
  • Discover new selective modulators of these channels, able to cross the blood-brain barrier, with the hope to design future interesting central nervous system medications

Recordings are usually performed in anaesthetized animals but recordings in awake animals are presently developed. A comparison between wild-type animals and transgenic animals is also possible.

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Preclinical GAIT analysis

The CatWalkTM XT system is a highly sensitive tool for quantitative assessment of footfalls and motor performance in unforced moving animals such as rats, mice and guinea pigs.

Catwalk Souris

It can be used to evaluate any experimental model/procedure that affects the locomotor ability of rodents (i.e. genetic, chemical, physical injury to the central nervous system, peripheral nervous system or skeletal or muscle functioning). More specifically, its use has been validated for spinal cord injury and other nerve injuries, neuropathic pain, arthritis, stroke, Parkinson’s disease, cerebellar ataxia, traumatic brain injury and peripheral nerve damage.

3D Analysis Catwalk

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Preclinical imaging

Logo_Logo-autres_GIGAOur GIGA platforms offer advanced preclinical functional and anatomical imaging solutions for a broad spectrum of application fields.

Our range of techniques includes:

Magnetic resonance imaging (MRI) scanners use strong magnetic fields and radio-waves to visualize detailed internal structures. Images are obtained in vivo with very high spatial and temporal resolution, good contrast for brain and soft tissues. MRI can be used in a wide variety of applications including anatomical, functional (fMRI) and molecular imaging for medical diagnosis, staging of disease and for follow-up without exposure to ionizing radiation.

Our system, Agilent MicroMRI 9,4T 310 ASR, is equipped with a technical imaging unit (MINERVE). It ensures the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

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Computed Tomography (CT) is a non-destructive technique that yields structural and anatomical high-resolution 3D images with limited or no sample preparation required. This imaging modality complements the metabolic or functional images obtained with PET.

Being equipped with two beds for mice (25 mm) and rats (75 mm), our system, the TriFoil Imaging eXplore CT 120 micro-CT, is designed to visualize, quantify and characterize anatomical parameters in small animals. The system is also equipped with a technical imaging unit (MINERVE), ensuring the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

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Positron Emission Tomography (PET) has the sensitivity at picomolar level to visualize molecular processes in 3D. In vivo PET imaging with labelled lead compounds will help to select the best one for clinical trials.

 

The technique allows:

  • The collection of quantitative and dynamic biodistribution data (e.g. micro-dosing studies) at an early stage of the clinical development: dynamic data for in-depth kinetic modeling, online blood measurements and in-brain positron-emission measurements
  • Detailed drug occupancy studies (proof of targets, mechanism, efficacy, pharmacokinetics, biodistribution)
  • Concentration analysis of targeted analytes after having developed and validated a dedicated method using microdialysis, a technique used for continuous measurement of free, bound analyte concentrations in the extracellular fluid. Analytes may include endogenous molecules (e.g. neurotransmitter, hormones, glucose, etc.) to assess their biochemical functions in the body, or exogenous compounds (e.g. pharmaceuticals) to determine their distribution within the body)

We are authorized to conduct research programs with classical (18F-FDG) and original radiotracers. Furthermore, we have developed expertise in experimental design, data collection, correction and modeling for kinetic analysis.

Being equipped with two beds for mice (25 mm) and rats (75 mm), our system, the Siemens Concorde FOCUS 120 micro-PET, is designed to visualize, quantify and characterize anatomical parameters in small animals. The system is also equipped with a technical imaging unit (MINERVE), ensuring the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

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Our equipment includes the high-resolution, high-frequency ultrasound imaging system Vevo 2100 (Visualsonics). This is a non-invasive, in vivo micro imaging system, enabling visualization, assessment and measurement of anatomical structures and hemodynamic function in longitudinal studies for small animal phenotyping.

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The Xenogen IVIS 200 system is a highly sensitive and flexible system to trace bioluminescent reporter genes both in vivo and in vitro. It allows non-invasive longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in living animals. By performing spectral fluorescence imaging, it allows the simultaneous use of bioluminescence and fluorescence imaging.

Bioluminescence imaging uses the enzyme, luciferase, that can be inserted into the genome of cancer cells or the cells you wish to track. Once these cells are implanted within mice, a tail vein or intra-peritoneal injection of luciferin (luciferase substrate) allows to follow their distribution ex vivo without euthanasia.

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Intravital microscopy is an extremely powerful tool that enables imaging several biological processes in living animals. In particular, to analyze:

 

 

  • Recruitment processes of leukocytes and platelets on microvessel endothelia
  • Bacterial adhesion on the microvessel endothelia
  • Thrombi and vascular occlusion formation
  • Lymphocytes migration to lymph nodes and lymphocytes adhesion to endothelia

Our equipment includes a motorized Olympus Cell R (Upright) microscope with EMCCD camera, controlled via the Slidebook software.

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PXI X-RAD SmART Image Guided Irradiator combines 3D imaging with highly accurate radiotherapy for Small Animals: mice, rats and rabbits. It combines a user friendly interface with state-of-the-art Monte Carlo calculation algorithms to rapidly devise treatment plans.

The system is fully integrated, with automated CT-CT registration, allowing, Image Guided Radiotherapy for precise tumor/organ localization. The integrated treatment planning enables rapid and highly conformal radiotherapy treatments, with collimator from 1 mm to 10 cm in round and non-round shapes, to be delivered in any scenario, ranging from simple subcutaneous xenografts to complex metastatic models or to develop non tumoral model as radiation-induced injury for a specific purpose.

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