Cancer is the over-production of cells in the body which can spread through the organs and lead to health complications and possible eventual death. There are different types such as lung, breast, liver, stomach and throat.

Cancer can be caused by infections, exposure to harmful chemicals, radiation as well as lifestyle risk factors such as smoking tobacco, excessive alcohol use, lack of exercise and unhealthy diets. Approximately 8.2 million people die from cancer every year. Early diagnosis and treatment can help to reduce the risk of fatality so having instruments that tell us more about the cells is critical.

Scientific researchers, typically chemists and biochemists, are investigating how cancer develops in the body so that further methods can be used to prevent it spreading. Nuclear Magnetic Resonance (NMR) is a useful tool in cancer research because of the role that metabolism plays in cancer. Researchers globally are using the technology to investigate the cell in cancers such as lung, renal and breast cancer.

An NMR spectrometer instrument can help researchers to categorize metabolites, the intermediates and products of metabolic processes in a biological system based on the magnetic properties of their nuclei. Biomarkers of metabolism can be the metabolites detected in urine or blood cells.

Why metabolites are important

Defining metabolites is important to cancer research. German scientist Otto Heinrich Warburg discovered a link between cancer and metabolism. Mutations in cancer genes and alterations in signals from cells can trigger a change in metabolism.

This provides an indication for the presence of cancer. Cancer tumor cells can continue to convert glucose to lactate even when oxygen is present – aerobic glycolysis. This helps to differentiate them from normal cells.

The role of NMR

An NMR spectrometer can help to identify quantitative and structural characteristics of organic matter such as lactate produced from cancer cells converting glucose. It does this by focusing on the magnetic properties of the nuclei of atoms.

All living matter contain cells which have atoms. Each atom has a nucleus that contain subatomic particles called electrons (negatively charged particles), protons (positively charged particles) and neutrons (neutral particles). The charge of an atom depends on how many of each of the different types of subatomic particles it has.

An NMR spectrometer investigates atoms by using its magnet to create a magnetic field that impacts the nuclei of atoms in different ways due to their individual charges. The results are plotted on a diagram showing NMR spectra – the peaks created for separate constituents of the nuclei. This helps scientists to derive the chemical structures.

NMR has low sensitivity and high limits of detection for metabolites. Sometimes it is difficult to determine the details of a sample if there are low levels of metabolites. Hyperpolarized NMR has been used to characterize metabolism through tracing metabolites in vivo. At times hyperpolarization has helped to increase sensitivity by 10,000 when a sample has very low concentration that they are almost out of detection ranges.

A positive aspect of NMR is that samples are not destroyed by the process so that they can be analyzed in other ways.

The history of NMR Spectrometer

German physicist Gunther Laukien was a pioneer in NMR spectrometer instruments. He formed the Bruker Company after his post-doctoral research into NMR spectroscopy and paper on the relevance of the technique. He helped to construct the impulse spectrometer. He developed the first fully transistorized NMR instrument during the 1960s.

The instruments have been continually developed and NMR spectrometers now provide us with ways of identifying tumor burden, disease progression and metastases amongst other processes. They are commonly used with mass spectrometers to provide us with more details about a metabolome.

Bruker remains one of the key manufacturers of NMR spectrometers. Companies such as Varian have had a history in the field too and there are other companies producing instruments such as Magritek and JEOL.

References:

• Otto Heinrich Warburg: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1931/warburg-bio.html
• Otto Warburg’s contribution to current concepts of cancer metabolism: http://www.ncbi.nlm.nih.gov/pubmed/21508971
• Tumor Metabolome: http://www.metabolic-database.com/html/aerobic_glycolysis.html
• Nature metabolomics: http://www.nature.com/subjects/metabolomics
• Applications of metabolomics in cancer research: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709411/
• World Health Organization facts and figures on cancer: http://www.who.int/cancer/en/

On the Web:

• Metabolomics in general http://www.nature.com/subjects/metabolomics
• History of Bruker Corporation: https://www.bruker.com/about-us/who-we-are/whoweare/history.html
• Hyperpolarised NMR of plant and cancer cell extracts at natural abundance: http://pubs.rsc.org/en/Content/ArticleLanding/2015/AN/C5AN01203A#!divAbstract
• Gunther Laukien: http://www.chemheritage.org/visit/events/awards/affiliate-partnership-awards/pittcon-hof-laukien.aspx

Further Reading

• All Nuclear Magnetic Resonance (NMR) Content
• Future of NMR Spectroscopy
• Applications of In-Cell NMR
• NMR-Based Metabolomics
• 2D NMR Spectroscopy: Fundamentals, Methods and Applications

Written by

Deborah Fields

Deborah holds a B.Sc. degree in Chemistry from the University of Birmingham and a Postgraduate Diploma in Journalism qualification from Cardiff University. She enjoys writing about the latest innovations. Previously she has worked as an editor of scientific patent information, an education journalist and in communications for innovative healthcare, pharmaceutical and technology organisations. She also loves books and has run a book group for several years. Her enjoyment of fiction extends to writing her own stories for pleasure.