Neuropsychiatric disorders such as schizophrenia, depression, and Parkinson’s disease are typically associated with large imbalances in neurotransmitter levels. Dopamine, in particular, is likely central to the pathophysiology of these diseases, but we currently lack a robust means of measuring dopaminergic system health. We have previously developed a class of small molecule fluorescent false neurotransmitters (FFNs) to image dopamine storage and release in vitro and ex vivo. Recently, FFNs were used to measure norepinephrine release in vivo via cranial window in mice. Dopamine’s predominance in the striatum and midbrain however limits our ability to image FFNs in these areas using fluorescence microscopy. Instead, we have begun characterizing magnetic resonance false neurotransmitters (MFNs) for use with magnetic resonance spectroscopy (MRS) in mice. These probes have an ethylamine group to target the dopamine active transporter (DAT) and vesicular monoamine transporter (VMAT2) as well as a 19-fluorine handle located adjacent to a pH-sensitive phenol group. With this strategy, the fluorine nucleus will have a different chemical shift when sequestered in synaptic vesicles (pH ~ 4.5) than when in the cytoplasm or extracellular milieu (pH ~ 7.4) making the two populations distinct and quantifiable. We have characterized promising candidates in solution, in cell culture, and in acute mouse slice, and have started initial experiments in vivo on a 9T MRI/S.

Development and characterization of a 19F-MRS dopamine sensor

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.