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OISM Mass Spec Method Aims to Provide Early Detection of Heart Disease, Breast and Prostate Cancer

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NEW YORK (360Dx) – A procedure described in the fall issue of the Journal of American Physicians and Surgeons takes aim at enabling a single test that could provide early detection of heart disease, breast cancer, prostate cancer, and other medical conditions.  

The research — which originated decades ago and has advanced during recent years partly because of the application of advanced mass spectrometry — is showing clinical promise and could eventually yield a commercial service that enables patients to access a broad range of diagnostic information for around $5, Jane Orient, a physician, faculty member of the Oregon Institute of Science and Medicine (OISM), and the managing editor of the Journal of American Physicians and Surgeons, said in an interview.

However, it could take several years for a commercial service based on their metabolic profiling technique to be made available, Orient said. The researchers need to first expand their bank of urine samples, which would facilitate developing diagnostic profiles for a far broader number of medical conditions, she added.

In their study, researchers at non-profit OISM reported that about 90 percent of people who experienced a cardiac event had a specific pattern present in a urine specimen from 4 to 30 months before the diagnosis of heart disease. The researchers noted that similar diagnostic patterns were present in urine samples from people with breast or prostate cancer.

During their research, the researchers used magnetic resonance mass spectrometry (MRMS) to quantitatively analyze urine samples periodically from people who have experienced similar medical events.

MRMS permitted the simultaneous quantitative measurement of more than 800 molecular urinary constituents of human metabolic origin, the researchers said. During a 7-minute run using MALDI mass spec combined with MRMS, they measured more than 100,000 different chemical constituents from a 5-microliter urine sample in positive ion mode.

The OISM group mathematically combines information from the substances they measure and produces a diagnostic coefficient for each condition of interest.

Arthur Robinson, one of the investigators in the current study, and his colleagues at the University of California at San Diego, Stanford University, and the Linus Pauling Institute of Science and Medicine, developed quantitative metabolic profiling during a project that ran from 1968 to 1978.

With an objective of developing a method for low-cost, mass screening of people to increase their quality and length of life, the researchers used mostly chromatographic measurement of between 50 and 150 substances in human body fluids and tissues and then applied computerized pattern recognition. They developed unique profiles for multiple sclerosis, Duchenne dystrophy, Huntington's disease, breast cancer, diet, fasting, sex, diurnal variation, and chemical birth control.

They also noted that recent research has helped them overcome some of the project's initial limitations. Advances in mass spectrometry enabling fast and low-cost simultaneous measurement of thousands of substances, for example, solved the challenge of having to implement slow and expensive analytic procedures. Additionally, when people donated multiple samples over an extended period of time, they served "as their own controls and markedly enhanced the precision of the metabolic profiles," the researchers said.

The OISM urine bank, which has been in operation since 2013, exists for that purpose, and in the JAPS study, the researchers presented the first set of results from the project.

The researchers are now combining two forms of mass spectrometry to conduct rapid metabolic profiling. One form, Fourier transform ion cyclotron resonance mass spectrometry, provides extremely high resolution and high mass measurement accuracy; and the other, matrix-assisted laser desorption ionization (MALDI), provides rapid profiling analysis, the researchers said.

High-resolution measurement enables detection and quantification of thousands of independent chemical substances in a single sample, and works without the need for separation prior to measurement. The researchers noted that the technique provides the ability "to discern the extensive metabolite information generated from the ionization of urine samples, while providing a unique speed advantage."

OISM noted that when a certain number of subjects develop a condition of interest, the researchers begin analysis of the samples.

The ability to develop additional patterns depends on the number of samples donated to the urine bank and the willingness of people to show up frequently to provide samples and general information about their medical health, Orient said. The bank is currently working with frozen urine samples from around 5,000 donors.

"If you could expand it to 15,000 samples over several years, there would be enough to develop profiles on a whole lot of illnesses," Orient said.

As this bank is expanded and matures, it might make it possible to discover profiles for less prevalent diseases, she added.

The researchers said that they hope to eventually develop a single, affordable test that has the potential to determine the probability of most diseases. The service would provide competition for existing laboratory-based tests, including those provided by reference laboratories, Orient said.

"With one single procedure, it would test for anything for which a profile has been developed, Orient said. "This would be a one-stop, one-test service."

The technique is currently only available for research and its information cannot be used in diagnosing or treating patients, the researchers said.

In the future, however, it could be made available through a sample kit containing "a suitable disposable laser desorption target on which the user places a drop of urine, allows it to dry, and then mails the target … to a central mass spectrometry laboratory," the researchers said.

Orient noted that "there would be a huge benefit to having this rolled out nationwide" and having a broader range of groups establish suitable urine banks. However, its scope is currently limited to what OISM can itself accomplish, she said.

Orient noted that the service is something that she would value as part of the "arsenal of things" that she could offer to patients.