The National Physical Laboratory (NPL), the Teddington-based institute that develops and maintains standards for the UK’s National Measurement System, is collaborating with GlaxoSmithKline to create a label-free molecular-imaging instrument capable of measuring intracellular drug distribution with unmatched spatial resolution.

This new instrument will be built by ION-TOF, the German manufacturer of innovative instruments for surface analysis such as time-of-flight secondary ion mass spectrometers, and housed at the UK’s National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), established by NPL and the University of Nottingham.  

The 3D nanoSIMS project, which the UK government’s Department of Business, Innovation and Skills will support with more than £4.5 million in funding from its Strategic Capability Programme of the National Measurement System, promises to help draw the line more accurately between efficacy and toxicity in drug development and eliminate late-stage pipeline failures.

Chemical labels

As things stand, NPL explained, imaging techniques cannot reach beyond micron resolution without adding special chemical labels to drug molecules. These labels can significantly affect the behaviour of the drug, introducing too much uncertainty into the image generated. 

The aim of the 3D nanoSIMS project is to provide label-free molecular imaging in three dimensions by enhancing imaging sensitivity by a factor of 100 and increasing spatial resolution to 50 nanometres.

Measuring intracellular drug distribution is a significant challenge for the pharmaceutical industry, NPL points out.

By helping to identify where drugs go at the cellular level, even within specific organelles, the new instrument could answer long-standing questions about whether drug concentrations are “sufficiently high in the right places to have a therapeutic effect, or if the medicine is lodging within cellular components and causing toxicity”, it comments.

Reduce failures

If these anomalies were spotted earlier, NPL adds, “it might help to explain toxicities or lack of efficacy of a medicine and reduce costly late-stage failures”.

Designing compounds that are specific for molecular targets “is part of drug development but knowing that they reach their target molecule in the right amount at the right place in the right cells is only just beginning to be attainable in intact cells within tissues”, commented Sir Colin Dollery, who acts as a senior research and development consultant to GlaxoSmithKline. 

Along with NPL, GSK and ION-TOF, the 3D nanoSIMS project involves Professors Morgan Alexander, Martyn Davies and Clive Roberts at the University of Nottingham School of Pharmacy as well as Professor Luke Hanley, head of the Chemistry Department at the University of Illinois, Chicago in the US.