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Investigación para el cáncer de la próstata 300 veces más sensibles que pruebas actuales

por Brendon Nafziger, DOTmed News Associate Editor | November 16, 2009
Men who have had their prostates removed but who still have cancer might be in for earlier diagnoses - and thus more effective treatment - if a new test using gold nanoparticles bristling with a DNA "barcode" pans out.

Researchers from Northwestern University have developed a screening test that's 300 times more sensitive to specific biomarkers for cancer than what is currently on the market.

Results from an early study of the test, initially designed for prostate cancer but which may apply to other conditions, including heart attacks, were published recently in the Proceedings of the National Academy of Sciences.
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Redefining zero

To determine if a man who has had a cancerous prostate removed is still at risk for cancer recurrence, doctors check his prostate-specific antigen (PSA) levels. While flatlined levels indicate the man's in the clear, rising levels of PSA after a radical prostatectomy suggest that cancer has returned, or is likely to.

The problem is that current tests are only sensitive to, at most, 0.1 nanogram of PSA per milliliter of fluid. While that sounds sensitive, such tests can actually miss the presence of ultra-minute levels of PSA, misleading patients that their PSA levels are at zero.

"But the conventional test results are not really at zero," Chad Mirkin, Ph.D. a professor of chemistry, materials science and medicine at Northwestern, tells DOTmed News. "It's just undetectable. Everybody post-prostatectomy has a measurable level of PSA. When a doctor says you have a zero PSA rating after a prostatectomy, he doesn't mean you really have zero PSA. You just have undetectable levels."

This distinction is important, Dr. Mirkin says, because if you can detect rising PSA levels before current technology now allows, you could identify people at risk for cancer recurrence while there still might be time to treat them with so-called salvage therapies.

You can also reassure the approximately 58 percent of men whose prostates were removed and won't have recurrence that they have nothing to worry about. "You can take the weight of the world off the shoulders of folks who are not going to recur," he says.

That's why Dr. Mirkin hopes his test will "redefine zero" so when doctors tell patients the antigen count is stable or virtually absent, it really is.

Reading the DNA barcode

And these accurate diagnoses will come about thanks to a test made from infinitesimally tiny gold nanoparticles outfitted with biological sensors.

Dr. Mirkin and his colleague, Shad Thaxton, M.D., a urologist at Northwestern's medical school, create the screening tests by covering gold nanoparticles with identical strands of DNA, or "barcode DNA." Attached to this barcode are antibodies that can capture PSA, and in the assay are also magnetic particles that can sandwich the PSA into the barcode. After running a sample through the test, the magnetic particle-PSA sandwiches are pulled out of the solution with a magnetic field, the gold particle is dissolved, and the PSA levels can be calculated.

The study published this week is a retrospective one, done on samples already harvested from 18 people. Another study, which Dr. Mirkin hopes to have finished this fall and published in the next six to nine months, is also retrospective but covers 250 patients.

More applications

Dr. Mirkin believes his test will have uses other than with post-op prostate cancer patients. Currently, Nanosphere, a company he founded and whose board he sits on, is researching a similar device that would provide early detection of heart attacks by looking for minuscule levels of a protein, troponin I, the heart muscle sheds into the bloodstream when damaged.

"Hospitals spend a huge amount of money and shelf space to differentiate early stages [of heart attacks] from indigestion. You monitor patients for hours, sometimes admit them, and it costs thousands and thousands of dollars for each patient," he says. "And if you don't do this, you [might] send people home who ultimately die of a heart attack."

But he hopes this test will both save lives and save hospitals money. The device is in clinical development, but Dr. Mirkin predicts it will be complete by next year.