Journal
NEUROIMAGE
Volume 172, Issue -, Pages 808-816Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2018.01.013
Keywords
Mass spectrometry imaging; Blood-brain barrier; Drug-drug interactions; Elacridar; Loperamide; Propranolol
Funding
- Swedish Research Council [2013-3105, 2014-6215]
- Swedish Brain Foundation
- Swedish Foundation for Strategic Research [RIF14-0078]
- AstraZeneca
- Science for Life Laboratory (SciLifeLab)
- CAPES - Coordination for the Improvement of Higher Education Personnel
- ARIADME (European FP7 ITN Community's Seventh Framework Program) [607517]
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There is a high need to develop quantitative imaging methods capable of providing detailed brain localization information of several molecular species simultaneously. In addition, extensive information on the effect of the blood-brain barrier on the penetration, distribution and efficacy of neuroactive compounds is required. Thus, we have developed a mass spectrometry imaging method to visualize and quantify the brain distribution of drugs with varying blood-brain barrier permeability. With this approach, we were able to determine blood-brain barrier transport of different drugs and define the drug distribution in very small brain structures (e.g., choroid plexus) due to the high spatial resolution provided. Simultaneously, we investigated the effect of drug-drug interactions by inhibiting the membrane transporter multidrug resistance 1 protein. We propose that the described approach can serve as a valuable analytical tool during the development of neuroactive drugs, as it can provide physiologically relevant information often neglected by traditional imaging technologies.
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