The National Physical Laboratory (NPL), working with GlaxoSmithKline, has initiated 3D nanoSIMS, a project to develop a label-free molecular imaging instrument with spatial resolution capable of measuring the intracellular drug distribution. The project will receive more than £4.5 million (approximately $7.4 million) of funding from the Strategic Capability Program of the National Measurement System of the U.K. Government’s Department of Business, Innovation, and Skills.

According to NPL, imaging techniques cannot image beyond micron resolution without adding special chemical labels to the drug molecule. These labels can significantly affect the drug’s behavior giving too much uncertainty in the image, the company said. This project aims to provide label-free molecular imaging in 3D through enhancing imaging sensitivity by 100 times and increasing the spatial resolution to 50 nm.

A major challenge to the pharmaceutical industry is the measurement of the intracellular drug concentration. This new instrument could potentially help identify where drugs go at the cellular level, even within specific organelles, answering questions about whether drug concentration are sufficiently high in the right places to have a therapeutic effect, or if the medicine is lodging within cellular components and causing toxicity. Spotting anomalies earlier might help explain toxicities or lack of efficacy of a medicine and reduce costly late-stage failures.

The project brings together ION-TOF, a manufacturer of mass spectrometers for imaging, with professors Morgan Alexander, Martyn Davies, and Clive Roberts at the University of Nottingham School of Pharmacy and professor Luke Hanley at the University of Illinois at Chicago. ION-TOF will build the new instrument, which incorporates the Thermo Scientific Orbitrap mass analyzer for high-performance identification of substances.

The instrument will be based at The U.K.’s National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), established by NPL and the University of Nottingham. In addition to enabling new drugs and medicines research, this instrument could potentially benefit other fields including biomaterials, medical devices, regenerative medicine, and next generation plastic electronics for displays.

“GlaxoSmithKline scientists are looking forward to the opportunities the new equipment will provide to explore in detail the sites of action of novel drug molecules within single cells,” said Sir Colin Dollery adviser to the chairman of R&D and member of the Global Safety board at GSK. “Designing drugs 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. This ability will be a great opportunity.”

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