A three-minute test to diagnose prostate cancer “could save thousands of lives a year”, the Daily Express has said. The technique mixes a small amount of prostate gland fluid with a light-emitting chemical. The amount of light produced indicates levels of the natural substance citrate found in the fluid. Lower citrate levels are found in prostate cancer tissue than in normal prostate tissue.
This research is at a very early stage. Although the new method was able to measure the level of citrate in small amounts of prostate fluid, it has so far only been tested on samples from a small number of healthy men, and not men with prostate cancer.
Also, although other studies have shown that citrate is reduced in men with malignant prostate cancer, this method will now need to be tested further to see if it can accurately differentiate between prostate fluid from men with cancer and healthy men. If successful in such studies, the technique would need to be compared with established methods for detecting prostate cancer. It is too early yet to know whether this method will be effective for the detection or monitoring of prostate cancer, whether it will save lives or how much it would cost.
Where did the story come from?
Dr Robert Pal and colleagues from Durham University and the University of Maryland carried out this research. The study was funded by a number of organisations including the Engineering and Physical Sciences Research Council, the National Institutes of Health in the US, the Diagnostic Molecular Imaging research group and The Royal Society. The study was published as a communication in the peer-reviewed scientific journal Organic & Biomolecular Chemistry.
What kind of scientific study was this?
This was a laboratory study aimed at developing a test for measuring levels of two chemicals called lactate and citrate in bodily fluids.
The authors report that citrate levels are consistently lower in malignant prostate cancer tissue and, therefore, measuring levels of this chemical could be useful in screening for prostate cancer and monitoring progression of the disease. Citrate is a natural chemical produced and broken down in our cells as part of energy production. Lactate is another natural chemical, produced when our cells use glucose in conditions of no or low oxygen. Measuring lactate is important in sports medicine and in other medical situations.
The researchers wanted to develop a method of measuring lactate and citrate that would work on small amounts of biological fluids such as blood, urine, prostate fluid or semen.
They developed a method based on the reversible chemical binding of lactate and citrate (which are negatively charged molecules) to light-emitting compounds based on the element europium (Eu). These light emissions change when the light-emitting compounds bind to citrate and lactate.
The researchers made a number of salt solutions containing varying lactate and citrate levels, and mixed them with the europium compounds, looking at how their light emissions (luminescence) changed with each chemical. They also repeated this test using a simulated prostate fluid solution containing lactate, citrate and various salts and proteins, which was similar in chemical composition to real prostate fluid.
The researchers also used these tests to determine how strongly lactate and citrate bound to slightly different europium compounds. The researchers selected the compounds that performed the best in these tests to take forward to testing with biological fluids: one compound that bound to citrate much better than to lactate and one that bound to lactate much better than citrate.
The researchers mixed solutions with increasing concentrations of lactate or citrate in the simulated prostate fluid and measured the changes in light emission when these were added to the europium compounds. This allowed them to plot a graph showing how light emission changed in relation to increasing concentrations of lactate or citrate. This graph could be used to estimate concentrations of lactate or citrate in other solutions.
In order to test this, the researchers took samples of urine, seminal fluid (the fluid component of semen), prostate fluid, serum (the fluid component of blood) and saliva, measuring the levels of lactate using established methods. They then tested the lactate levels in these fluids using their light emission methods, and compared results. Similar experiments were performed using the europium compound that bound tightly to citrate to measure citrate concentrations.
The researchers then took 17 samples of prostate fluid from healthy male volunteers and measured the levels of citrate in these samples using established methods. These methods used 25 times the volume of fluid than was needed in the new test, which typically used a one-microlitre sample. The samples were then assessed using the new europium citrate test. The new and established tests were also used to determine levels of citrate in urine from healthy volunteers.
What were the results of the study?
The researchers found that their light emission test gave lactate concentrations in the biological fluids tested (urine, seminal fluid, prostate fluid and serum) to within 10% of the measurements taken with established methods. The test correctly identified the absence of lactate in saliva.
The new test also managed correctly to determine the levels of citrate in the prostate fluid of 17 healthy male volunteers, accurate to within 10% of the measurement using established methods. Similar results were found when comparing the new and established tests for measuring citrate levels in urine.
What interpretations did the researchers draw from these results?
The researchers conclude that they developed a rapid (less than five minutes) luminescence test to determine the concentration of citrate or lactate in small volumes of biological fluids.
They say that, in the case of citrate, the level of this chemical could be used to “confirm or indicate the onset or progression” of prostate cancer.
What does the NHS Knowledge Service make of this study?
This research is at a very early stage, and although the test has been able to measure the level of citrate in small amounts of prostate fluid this was on samples from a small number of healthy men. The technique developed in this preliminary research will now need further testing to see if it can accurately differentiate between prostate fluid from healthy men and men with prostate cancer.
It will also be necessary to determine whether the method would be able to detect cancer at an early enough stage for treatment to be effective. Even after this, the method would also need to be compared with existing tests, such as the prostate specific antigen (PSA) test, to see how it compares.
It is too early as yet to know whether this test will be effective for the detection or monitoring of prostate cancer, whether it will save lives or how much it would cost.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
Daily Express, 19 May 2009
BBC online, 18 May 2009
Daily Mail, 19 May 2009
The Daily Telegraph, 19 May 2009
Links to the science
Org. Biomol. Chem., 2009, 7, 1525 – 1528