FP6Individual fellowship2007–2009

ZNMOLIMAGE · Molecular imaging of zinc in the brain

FP6 — Marie Curie Actions (Human Resources and Mobility)

Duration
2007-05-01 → 2009-04-30
EU contribution
€195,173
Participants
1
Scheme
EIF

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Results in brief

Final Activity Report Summary - ZnMolimage (Molecular imaging of zinc in the brain)

The project concentrated on dynamic imaging of small animals and development of new type of positron emission tomography (PET) and imaging methods. We designed a protocol of dynamic imaging, i.e. a sequence of short duration frames showing evolution of radioactive tracer distribution like a video film, using short axial field of view scanner. The frames of the heart and brain were taken alternately and were then processed to extract the concentration of the tracer in blood plasma from the image of the left heart ventricle. The blood plasma concentration of the tracer was the input to kinetic modelling of the tracer concentration in the brain. The protocol was applied to glucose consumption measurement in various nuclei in the brain, using a glucose radioactive fluoro(18F)deoxyglucose (18-FDG) analogue for the rats over-expressing inducible cAMP early repressor (ICER) in neurons in search of the phenotype. This immediate early gene was involved in neuronal plasticity and was found as regulator of susceptibility to epilepsy. After brain stroke, some neurons die within the first few hours, whereas others are stressed by the event, but can be saved with proper pharmacological treatment, therefore it is important to delineate them as soon as possible. This area is called penumbra. We found that 18-FDG PET and corresponding magnetic resonance imaging (MRI) of the brain in the rat model of the disease might reveal the penumbra area. The area where glucose consumption was reduced by 50 % or more and no visible damage could be found in MRI was the penumbra area. Finally, during the project, a prototype scanner from Oncovision, Spain was developed, thoroughly tested and ‘matured’.

Data: CORDIS, © European Union

Project objective

The number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be the calcium of the twenty-first century (Nature Rev. Neurosci. June 2005, vol. 6, 449-62). Up to now, Zn can be detected only in vitro and with limited accuracy, due to non-specific reaction of Zn chelators, which react also with Ca2+.Recently, some new fluorescent probes for Zn2+ were developed with increased Zn2+ specificity. 62Zn-EDDA was the only known to me Zn radiotracer used in PET monitoring of pancreas activity in dogs. PET registration in vivo of placement and dynamics of Zn containing proteins and small molecules will not have the same resolution as in vitro, but offers many advantages, among the most important, that the animal is its own control, and it is tested alive.I would like to develop and implement new PET radiotracer based on 62Zn, 63Zn or 65Zn that would allow in vivo registration of Zn2+ transport in the brain of small animals. The same isotopes will be used for imaging in vitro together with new Zn specific fluorescent probes.One of the areas of application will be research on expression of matrix metalloprotease 9 (MMP-9), which contains Zn in active site and structural Zn and Ca. The role of MMP-9 in plasticity of the brain was subject of my recent neurobiological research.

Original text from CORDIS.

Participants

  • UNIVERSIDAD COMPLUTENSE DE MADRID · MADRIDCoordinatorSpain

Links

Data: CORDIS, © European Union