Top Rounded Image
20 October 2009 Northwestern University

Measureable PSA Levels Found in Post-Op Prostate Patients

Coloured scanning electron micrograph of two prostate cancer cells in the final stage of cell division.
Coloured scanning electron micrograph of two prostate cancer cells in the final stage of cell division..
Image Credit: VVG/Science photo library .

A team of Northwestern University researchers, using an extremely sensitive tool based on nanotechnology, has detected previously undetectable levels of prostate-specific antigen (PSA) in patients who have undergone radical prostatectomy.

The researchers found measureable PSA levels in each post-operative patient in its study, thanks to the power of the nanoparticle-based bio-barcode assay developed at Northwestern. The technology is 300 times more sensitive than commercially available PSA tests. After the removal of the prostate gland, patients typically have PSA levels that are undetectable when measured using conventional diagnostic tools.

This ability to easily and quickly detect very low levels of PSA may enable doctors to diagnose men with prostate cancer recurrence years earlier than is currently possible. Prostate cancer is the second leading cause of cancer death for men in the United States. (Only lung cancer is more deadly.)

"We have defined a new zero for PSA," said Chad A. Mirkin, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, professor of medicine and professor of materials science and engineering. "This level of sensitivity in detecting low concentrations of PSA will take the blinders off the medical community, especially when it comes to tracking residual disease."

The study will be published online during the week of Oct. 19 by the Proceedings of the National Academy of Sciences (PNAS). Mirkin and C. Shad Thaxton, M.D., assistant professor of urology in Northwestern's Feinberg School of Medicine, led the study. (Both are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.)

"This new PSA assay may alter the management of patients who have been treated with surgery for prostate cancer," said William J. Catalona, M.D., professor of urology at the Feinberg School and director of the Clinical Prostate Cancer Program at the Lurie Cancer Center. He was the first to demonstrate that the PSA test, a simple blood test, could be used as a screening tool for prostate cancer.

"Studies have shown that postoperative radiation therapy given early to patients with adverse pathology, called adjuvant radiation, reduces the recurrence rate and improves survival," Catalona said. "Because the ‘nano-PSA assay' is more sensitive than the current commercially available PSA tests, it may allow physicians to target adjuvant radiation for patients destined to have a life-threatening tumor recurrence."

The study is an early indicator of how nanotechnology can be used to improve medical diagnostics and early cancer detection. In the case of prostate cancer recurrence following primary surgical treatment, patients with detectable but non-rising PSA levels could be reassured that their cancer will not recur. This reassurance potentially could be delivered much earlier than with conventional diagnostic tools. For patients with increasing levels of PSA, detected before conventional tools are able, doctors could diagnose a recurrence and intervene accordingly.

Furthermore, the effectiveness of post-operative treatment could be assessed by monitoring a patient's PSA levels. Tracking PSA levels early, before conventional tools are able, may allow doctors to validate treatments for recurrent cancer, such as radiation, hormone therapies and chemotherapies. The most effective will be able to keep down PSA levels.

"The first route to a new therapeutic is a good diagnostic tool, and that's what we have here," said Mirkin, director of Northwestern's International Institute for Nanotechnology. "This bio-barcode assay, or a variant of it, could be a commercial tool in as little as 18 months. The technology is there. Now it's a business decision."

PSA is a protein produced by the cells of the prostate gland and found in the bloodstream. This pilot study looked at serum samples from 18 post-prostatectomy patients collected over the course of a number of years.

The researchers were able to reliably and accurately quantify PSA values at less than 0.1 nanograms per milliliter, the clinical limit of detection for commercial assays. The lower limit of detection for PSA using the bio-barcode assay is approximately 300 times lower than the lower limit of detection for commercial tests. The PSA measurements were used to classify the patients as either having no evidence of disease or having a relapse of disease.

The Northwestern team is now conducting a similar retrospective study of 260 patients and eventually plans to do a large prospective study.

The ultra-sensitive technology is based on gold nanoparticle probes, decorated with DNA and antibodies that can recognize and bind to PSA when present at extremely low levels in a blood sample. A magnetic microparticle, outfitted with a second antibody for PSA, also is used in the assay. When in solution, the antibody-functionalized particles "recognize" and bind to PSA, sandwiching the protein between the two particles.

The key is that attached to each tiny gold nanoparticle (just 30 nanometers in diameter) are hundreds of identical strands of DNA. Mirkin calls this "bar-code DNA" because they have designed it as a label specific to the PSA target. After the "particle-protein-particle" sandwich is removed magnetically from solution, the DNA is removed from the sandwich and read using a Verigene® ID system, a nanotechnology platform designed to detect and quantify DNA.

The amount of PSA present is calculated based on the amount of bar-code DNA. For each molecule of captured PSA, hundreds of DNA strands are released, which is one of the ways the PSA signal is amplified.

Source: Northwestern University /...

Previous Story: Perfect Particles Hit the Nano Production Line
Next Story: New plastic optical fibre brightens up communications networks

Bookmark and Share

2 Comments

Comment Author Icon jim wood
Comment Date IconPosted on 2010-04-22 at 00:06:03
good study but does not answer my question. two years after my operation my psa is .02. can you give me some info. thanks

Reply

Comment Author Icon Lou
Comment Date IconPosted on 2014-05-07 at 20:51:22
Jim,

I’m 3 1/2 years post-op and my recent PSA was 0.19. Was being tested once a year after the first year, but now my doctor suggests once every six months because the PSA rose slightly from my last test in April of 2013.

Naturally, I don’t like it going up, but there’s an interesting article by Johns Hopkins that suggests guys like you and me need not panic. If your Gleason score was 7 or less and your PSA is 0.20 or less, a man has an 82% chance of not developing bone cancer over the next eight years. Basically, we have a 4 out of 5 shot at being OK.

Anyway, do check out the article by Dr. Walsh of Johns Hopkins. Hopefully it puts your mind at ease. I Googled "Post Op PSA scores" to access the article.

Good luck. We’re gonna live to be 100!

Reply

Leave a Comment

The Institute of Nanotechnology puts significant effort into ensuring that the information provided on its news pages is accurate and up-to-date. However, we cannot guarantee absolute accuracy. Consequently, the Institute of Nanotechnology disclaims any and all responsibility for inaccuracy, omission or any kind of deficiency in relation to the news items and articles hosted herein.

Bottom Rounded Image