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Zusammenfassung:
Amino acid neurotransmitters are considered as key biological messengers. Thus, their quantification and monitoring would allow a greater understanding of the molecular mechanisms associated with the function of the brain and the associated neurological disorders. Currently no method exists that can non-invasively determine the concentration of neurotransmitters in vivo. Magnetic resonance imaging (MRI) has recently been demonstrated as a promising method to monitor physiological events noninvasively, with high temporal and spatial resolution. Here, we address the issue of neurotransmitter monitoring through MRI by describing our progress towards the development of MR probes for tracking the change in neurotransmitter concentrations within the brain. We designed and synthesized two “turn-off” DO2A derived gadolinium based probes, which respond to changes in neurotransmitters concentrations at physiological pH. These complexes consist of a dual receptors, which on interaction with the neurotransmitters modulate their relaxivity. In vitro inversion recovery measurements were performed at physiological pH and at 60 MHz to monitor the changes in relaxivity upon the addition of neurotransmitters. Both GdL1 and GdL2 complexes showed a relaxivity change of up to 75% upon the addition of millimolar concentrations of certain neurotransmitters. Luminescence studies were also performed with EuL1 and EuL2 in the absence and presence of the same neurotransmitters. Changes in the europium emission spectra and a modulation of the hydration number (q) were observed upon addition of neurotransmitters for EuL1. The observed decrease in q was in good agreement with the change in relaxivity. These preliminary results give valuable insights into understanding the structural aspects of the contrast agent interaction with neurotransmitters and will help to improve the molecular design of new responsive agents. The financial support of the Max-Planck Society and the CNRS is gratefully acknowledged.
