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Abstract:
Calcium, present in high concentrations in the brain, plays an important role in neuronal signalling, e.g. through the transfer of charges between synapses, or triggering the release of neurotransmitters. It has been previously demonstrated that the concentration of Ca2+ changes significantly during neural activity.[1] However, used techniques are highly invasive and can only cover a small area of the brain at any moment with limited tissue penetration. Magnetic Resonance Imaging (MRI) on the other hand is non-invasive and allows the mapping of the whole brain at unlimited depths. To measure neural activity through changes in Ca2+ concentration using MRI, responsive contrast agents have been designed.[2] Recent reports of a system based on 3,2-hydroxypyridinone (3,2-HOPO) have demonstrated its attractive features as a contrast agent enabling this system to supersede current probes.[3] It exhibits high relaxivity values and a thermodynamic stability comparable with commercial agents. Moreover, it also has negligible interactions with interfering endogenous ions, despite the high number of coordinated water molecules. To the best of our knowledge there are currently no responsive probes based on this system. Therefore, we focused on the fusion of a 3,2-HOPO MR probe with a Ca2+ chelator. We show for the first time a facile synthesis to obtain a new HOPO-based MR-reporter without specialized equipment[3] and the introduction of a Ca2+ responsive moiety. We present the performance of this novel Ca2+ responsive probe from in vitro to more biologically realistic conditions. 1. Nicholson, C., et al., Calcium and potassium changes in extracellular micro-environment of cat cerebellar cortex. Journal of Neurophysiology, 1978. 41(4): p. 1026-1039. 2. Que, E.L. and C.J. Chang, Responsive magnetic resonance imaging contrast agents as chemical sensors for metals in biology and medicine.
