Expanding the Horizons of Imaging: Real-time Tracking of Drugs in the Brain

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

Many drugs fail in clinical trials despite showing promise in preclinical analysis. A key analytical challenge in this drug development breakdown is in measuring whether an effective dose of the administered drug reaches the right tissue at the correct time and for the required duration. As a result, mortality (death) rate is the metric most commonly used to judge whether a drug works. Hence, there is a clear need for new analytical workflows to be developed that can offer a detailed understanding of drug distributions in tissues.

We propose a new workflow using a combination of imaging approaches to determine drug distribution experimentally in vitro, in real-time in mice, and from excised tissue. For the purposes of method development, the distribution of a known brain tumour targeting drug will be investigated in mouse tissues and cells. In this workflow, magnetic resonance imaging (MRI) will be utilised for real-time imaging of drug distributions in the mouse brain. This technique will be supported by optical imaging via microscopy approaches and validated using mass spectrometry imaging of excised tissue samples from the same animal, allowing direct comparisons between the magnetic resonance, optical, and mass spectrometry imaging.

By combining these techniques, it will be possible to comprehensively showcase drug distribution in the brain in detail and in real-time. This workflow will be highly translational for the analysis of alternative drugs from various tissues.

Publications

10 25 50
 
Description Elected member of BMSS
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Feedback to UKRI on mass spectrometry funding
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Improved lipid analysis to inform future therapeutic strategies
Amount £75,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2022 
End 10/2025
 
Description Improved lipid analysis to study GBM
Amount £60,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2021 
End 10/2024
 
Description Microscopic-level molecular understanding of the neuro-chemical environment alongside functional MRI contrast agent penetration
Amount £4,480 (GBP)
Organisation Massachusetts Institute of Technology 
Sector Academic/University
Country United States
Start 01/2022 
End 07/2022
 
Description IBIN presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Conference presentation
Year(s) Of Engagement Activity 2021