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Dr. Pascal Kadjane

Address: Spemannstr. 38
72076 Tübingen
Fax: +49 7071 601 652

 

Picture of Kadjane, Pascal, Dr.

Pascal Kadjane

Position: Research Scientist  Unit: Alumni Logothetis

Development of 19F-labelled contrast agents for Ca2+ ion detection using MR-based techniques

Pascal Kadjane, Goran Angelovski, Gisela Hagberg, Nikos K. Logothetis

 

Introduction

Magnetic resonance imaging (MRI) is a non-invasive technique widely used in the biomedical science to visualize detailed internal structure. It provides 3D images without the use of ionizing radiation. To improve the image contrast, paramagnetic contrast agents (CAs) are utilized. Lately, considerable efforts are devoted to evolve 19F MRI probes for molecular imaging applications, in order to overcome the problem of background signal related to 1H MRI [1]. The lack of background signal along with the possible quantification and specific detection of 19F labels have encouraged scientists to develop fluorinated smart CAs capable of detecting a particular biological event. Such probes could have great importance for instance, for the tracking of Ca2+ concentration changes, as this ion is an essential messenger intervening in diverse biological processes.

 

Goals

The aim of the project is to synthesize different fluorine-containing probes that enable us to visualize the changes in extracellular Ca2+ concentration, during neural activity in the brain by means of 19F MRI. We developed molecules which undergo a conformational change in the presence of Ca2+ which brings the 19F reporter closer to the paramagnetic ion and causes an alteration of its signal.

 

Methods

The fluorine reporter is attached to a well studied Ca2+ chelator and the corresponding compound is conjugated to a cyclen based complexing cage. The synthesized probes are studied by means of NMR spectroscopy in order to determine the T1 and T2 of 19F. Phantom images of the probes are subsequently acquired in the absence and presence of Ca2+ to assess the potential application.

 

Initial results

Two fluorinated probes with different numbers of fluorine atoms have been synthesized. The systems have been metallated with four different paramagnetic lanthanide ions (Gd3+, Tb3+, Dy3+, Tm3+) and, the corresponding complexes have been characterized. They exhibit different magnetic features resulting in a tuneable 19F signal. For all complexes, we observed that the addition of Ca2+ engender a change of the 19F signal which is followed by a decrease of the 19F T1 and T2. The observed changes are reversible as the relaxation times return to their initial values upon addition of EDTA.

 

Initial conclusions

The synthesis of two 19F-containing ligands has been successfully performed. The spectroscopic studies of the probes revealed that the systems are sensitive to Ca2+, providing a new platform for development of quantitative and dynamic MRI.

 

References

1. Ruiz-Cabello J, Walczak P, Kedziorek DA, Chacko VP, Schmieder AH,Wickline SA, Lanza GM,  Bulte JWM (2008) In vivo hot spot MR imaging of neural stem cells using 19F nanoparticles Magnetic Resonance in Medecine 60(6) 1506-1511.

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Articles (3):

Kadjane P, Platas-Iglesias C, Boehm-Sturm P, Truffault V, Hagberg GE, Hoehn M, Logothetis NK and Angelovski G (June-2014) Dual-Frequency Calcium-Responsive MRI Agents Chemistry: A European Journal 20(24) 7351–7362.
Angelovski G, Gottschalk S, Milošević M, Engelmann J, Hagberg GE, Kadjane P, Andjus P and Logothetis NK (May-2014) Investigation of a Calcium-Responsive Contrast Agent in Cellular Model Systems: Feasibility for Use as a Smart Molecular Probe in Functional MRI ACS Chemical Neuroscience 5(5) 360–369.
Kadjane P, Logothetis NK and Angelovski G (April-2011) A straightforward and convenient pathway for the synthesis of functional bismacrocyclic ligands Tetrahedron Letters 52(14) 1619-1622.

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Last updated: Monday, 22.05.2017