Contact

Dr. Matteo Placidi

Adresse: TTR, Paul-Ehrlich- Str. 15
72076 Tübingen
Raum Nummer: E.2.131
Fax: 07071 601 919

 

Bild von Placidi, Matteo, Dr.

Matteo Placidi

Position: Postdoc  Abteilung: Alumni Logothetis

Development of neurotransmitter-responsive MR and optical imaging probes

 

Matteo Placidi

 

Introduction

The growth of MRI smart contrast agents is in line with current directions in molecular imaging, and could have a substantial impact on our understanding of both normal cognitive function and neurological disorders at a fundamental level [1]. The application of SCA whose signal varies as function of a given amino acid neurotransmitter allows us to investigate phenomena in any brain structure, as opposed to most fluorescence-based imaging methods, which are limited to depths of up to 1 mm.

 

Goals

The agents consist of lanthanide macrocyclic complexes conjugated to synthetic receptors for amino acids or mono amines, which change their magnetic properties in parallel with local concentrations changes of these neurotransmitters. Through the development of such agents, we aim to develop a technique to complement BOLD fMRI, to significantly increase the accuracy and specificity of non-invasive monitoring of neural activity.

 

Methods

Initially, the receptor site for these molecules was synthesised and linked to the reporter unit. Following their characterisation, the response of these complexes to a range of neurotransmitters was screened using NMR and luminescence spectroscopy. On obtaining a suitable and selective response their behaviour will be examined in a range of more competitive media including artificial cerebrospinal fluid. Ultimately, in vivo experiments in rats will be performed with the smart contrast agents exhibiting the most appropriate responses.

 

Initial results

Two types of SCA were synthesized: on-agents that allow the approach of water molecules which increases MR signal and hence tissue contrast and off-agents that displace water molecules decreasing MR contrast. A series of 8 (phosphonate based) on agents and 3 (guanidine based) off agents were synthesized. The 3 off agents gave the best response to the addition of neurotransmitters, with a decrease in the MR signal (relaxivity r1). However, suitable selectivity was not demonstrated. Pyrrole guanidinium agents also responded to neurotransmitters, showing an interaction at the receptor site (Figure 1).

 

Initial conclusion

Off agents appear more effective than on agents. Therefore such systems will be developed further with more receptor sites to enhance selectivity.

 

References

1.      Jasanoff A. (200) MRI contrast agents for functional molecular imaging of brain activity, Current Opinion in Neurobiology 17 593–600.

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Zeige Zusammenfassung

Artikel (2):

Placidi MP, Botta M, Kálmán FK, Hagberg GE, Baranyai Z, Krenzer A, Rogerson AK, Tóth I, Logothetis NK und Angelovski G (August-2013) Aryl-Phosphonate Lanthanide Complexes and Their Fluorinated Derivatives: Investigation of Their Unusual Relaxometric Behavior and Potential Application as Dual Frequency 1H/19F MRI Probes Chemistry - A European Journal 19(35) 11644–11660.
Placidi MP, Engelmann J, Natrajan LS, Logothetis NK und Angelovski G (September-2011) An aryl-phosphonate appended macrocyclic platform for lanthanide based bimodal imaging agents Chemical Communications 47(41) 11534-11536.

Poster (3):

Hagberg GE, Keliris A, Mamedov I, Placidi M, Merkle H, Logothetis NK und Scheffler K (April-23-2013): 19F-Lanthanide Complexes: T1 - and T2 - Dependent Signal Gain Using Gradient Echoes, 21st Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2013), Salt Lake City, UT, USA.
pdf
Hagberg GE, Mamedov I, Placidi M, Keliris A, Merkle H, Logothetis NK und Scheffler K (Oktober-29-2012): 19F-Lanthanide complexes: T1- and T2-dependent signal gain using gradient echoes, ENCITE Symposium "Red hot MRI: In vivo 19F imaging", Nijmegen, The Netherlands.
Placidi M, Engelmann J, Logothetis NK und Angelovski G (Februar-2012): Aryl Phosphonate-appended macrocyclic lanthanide complexes for application in bimodal imaging, 2011 World Molecular Imaging Congress (WMIC 2011), San Diego, CA, USA, Molecular Imaging and Biology, 14(Supplement 1) S92.

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Last updated: Montag, 22.05.2017