Metalloprotein-based contrast sensors for neurochemical detection by MRI

Noninvasive imaging methods to observe brain activity at a molecular level would be of significant benefit to neuroscience and the study of neurological disorders. To this end, we report several advances toward sensing biomolecules important in neurotransmission, neuromodulation, and inflammation by proton magnetic resonance imaging (1-H MRI). These approaches rely on exploiting the biomolecular specificity of naturally and artificially evolved protein binding pockets, as well as the natural and augmented proton spin relaxation effects of paramagnetic metalloproteins. Cytochrome P450 hemedomain mutants have been screened to reveal a set of turn-off MRI sensors for monoamine neurotransmitters with micromolar to submicromolar affinity, for which specific Type II ligand binding confers as much as a 93% change in T1 contrast enhancement at 4.7 T