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Detecting Metastatic Cancer Lesions… Before it is Too Late!

March 2009

By Julius Goepp, MD

Seeing Beyond Cancer

Seeing Beyond Cancer

The promise of improved tissue visualization using Combidex® is not limited to assessment of cancer and metastases. The remarkable ability of the USPIO particles in Combidex® to target macrophages means that they can, in principle, be used to identify any tissue in which these important inflammatory cells gather. That opens the door to a whole new world of functional diagnostic imaging, in which we look at how a tissue is performing in addition to simply what it looks like.

We’ve learned that much of the damage caused by ischemia (lack of blood flow) during strokes and heart attacks is related to inflammation in the tissue following the return of blood flow to the area.33-35 That idea, coupled with the inflammation-sensing abilities of Combidex® scanning, caught the imagination of a team of radiologists and neurologists at Heinrich-Heine-University in Dusseldorf. Finding that even high-resolution standard MRI did not allow them to discriminate between healthy and damaged tissue in rat brains following experimentally induced strokes,36 the team went on to study a small group of humans who had undergone naturally occurring strokes.37 Using Combidex® as a “cell-specific” contrast agent, the scientists went in search of the macrophages they knew must be infiltrating damaged tissue in the stroke victims. The patients received the Combidex® infusion at the end of the first week after the stroke, and had scans done twice over the next three days. Remarkably, the researchers found that they could identify changes in both blood vessels and in surrounding brain tissue. In this way they could actually watch as the inflammation-sensing macrophages made their way from the bloodstream into the damaged tissue, accurately tracking the location and the progress of the destructive inflammatory process. This landmark study marks the first time that physicians have been able to actually watch a stroke unfold before their eyes, with unprecedented detail, and to see precisely where and how much damage was occurring!

Combidex®—At Risk of Becoming an “Orphan Technology?

These researchers have now extended their work to pinpoint regions of developing inflammation in patients very early in an evolving stroke.13,15 These creative scientists concluded that “[Combidex®-] enhanced MRI may help to more specifically target anti-inflammatory therapy in patients with stroke,” potentially ushering in a new age of functional treatment as well as diagnosis for this widespread condition.

A less common but equally destructive condition, multiple sclerosis (MS) is also a result of inflammation in the brain, and the presence of macrophages in affected brain regions suggested the use of Combidex®-enhanced scans to French researchers in Bordeaux.11 They studied 10 patients with MS in acute relapses, conducting MR scans 24 hours after Combidex® injections. Thirty-three regions of brain inflammation were seen in nine patients, while similar regions showed up in only seven patients using conventional gadolinium-enhanced scans. The researchers concluded that Combidex® uniquely revealed cellular inflammatory events that were unfolding as the MS lesions were forming. As with the stroke studies described above, this offers a previously unheard-of ability to watch disease drama unfold—and perhaps ultimately, to administer targeted therapy.

Neurologists in Amsterdam have now extended that work in patients with MS, demonstrating that they can detect more brain lesions, earlier, with a USPIO-containing contrast agent than with standard scans.38 Studying 19 patients with fluctuating levels of disease activity, they identified 188 regions of brain inflammation, 144 of which were not identified on the standard scans. Areas of enhancement with the USPIO particles were evident earlier, and lasted longer, than lesions detected on the standard scans; this behavior suggests that the USPIO-enhanced scan is much more sensitive at demonstrating activity associated with inflammation in brain tissue—the researchers even speculated that they could see signs of tissue repair on some images!

Combidex®—At Risk of Becoming an “Orphan Technology?


Despite this extensive body of evidence favoring Combidex® in terms of effectiveness and safety, it is still not approved by the FDA or its counterpart in the EU. We asked Dr. Barentsz to comment on this situation. “This is an uphill battle,” he replies, “But one that I believe we can win. Physicians are notoriously slow to adopt new technologies, and frankly egos sometimes get in the way of progress. We need to get better-prepared and organized data in front of these regulatory agencies, and unfortunately they are becoming more, not less, bureaucratic over time.” Fortunately, because of his convincing studies, Barentsz himself is authorized to use Combidex® in scans at his facility in the Netherlands, and he continues to publish extensively on his successes.1,2,5,26,39

Can patients seek care voluntarily at Barentsz institution? “Yes, of course they can,” he says. “And in general I’ve found that, except for a few ‘dinosaurs,’ most surgeons and oncologists who’ve read the literature are willing to act on the results of our scans, which are read both by me and by an independent radiologist who’s familiar with the method.”


The discovery of the remarkable properties of ultra-microscopic iron particles, and their appeal to the inflammation-seeking macrophages, has opened new vistas for making functional diagnoses—diagnoses that show physicians not only the structures that comprise our bodies, but also their activities at an extraordinarily detailed level. Combidex®, the commercially produced MRI contrast-enhancing agent that contains these space-age particles, has proven its effectiveness and safety in numerous studies. The ability of oncologists to find and react to metastatic lesions previously too small or too isolated for detection will change the roadmap of cancer therapy, while neurologists and cardiologists can look forward to new ways of visualizing the destructive inflammatory changes that accompany cardiovascular disease, stroke, and other chronic conditions. There is still work to be done to achieve the widespread recognition that Combidex® deserves—the work of devoted clinician-researchers such as Dr. Jelle Barentsz is sure to achieve this in the near future.

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.

Bringing Combidex® Benefits to Those Who Need Them

Combidex® is not yet available in the US as a means of enhancing potentially life-saving MRI scans in men with prostate cancer—that’s why Dr. Jelle Barentsz and others testified recently at a US Senate hearing aimed at unblocking the bureaucratic process that’s holding things up.40 Fortunately, American patients still have access to the benefits of Combidex® scanning, thanks to a new organization called the International Strategic Cancer Alliance (ISCA). ISCA was formed to unite patients with oncologists and specialists who integrate a vast array of diagnostic approaches with synergistic therapies into individually tailored (boutique) treatment programs. ISCA is currently focused on assistance to newly diagnosed prostate and breast cancer patients. The leaders of ISCA include a network of subspecialized oncologists who are committed to helping patients navigate the medical world, in part by connecting them with cutting-edge technologies such as Combidex®, which show strong evidence of effectiveness in early detection of disease progression or complications.

“ISCA is working closely with the Life Extension Foundation to develop more meaningful insights into the all-important process of staging prostate cancers,” says Orn Adalsteinsson, PhD, the bioengineering expert who is CEO and one of the founders of ISCA. “Accurate staging is the key to setting therapeutic priorities and developing the best strategies for attacking prostate cancers,” he continues. “Lymph nodes that show up as positive on Combidex®-assisted scans are the earliest signs of cancers spreading outside of the prostate. When we can catch those ‘positive’ nodes, we are powerfully armed to attack a cancer before it has a chance to establish itself in other parts of the body, where metastases do their damage,” Dr. Adalsteinsson concludes.

Dr. Adalsteinsson works closely with Stephen Strum, MD, an oncologist with 20 years’ experience in treating prostate cancer patients. Drs. Strum and Adalsteinsson, working together, can provide a comprehensive early evaluation of newly diagnosed prostate cancer patients, and can devise a personalized diagnostic and therapeutic approach. When that approach demands the use of Combidex® scanning, the team arranges for the patient to see Dr. Barentsz in his facility in the Netherlands, and will then facilitate relay of the scans’ results back to the primary treating oncologists, complete with expert interpretation by Dr. Barentsz himself. “Cancer is a complex disease that requires a multi-prong effort to provide the best chances of attaining a cure, remission, or significant extension of life,” concludes Dr. Adalsteinsson. “At ISCA, we spearhead that effort and integrate effective modern techniques such as Combidex® to provide our patients with the very best opportunities.”

For further information, interested patients and family members can contactDr. Adalsteinsson at ISCA:

Orn Adalsteinsson, PhD, CEO 873 E. Baltimore Pike #333, Kennett Square, PA 19348

Phone: 610-628-3419

FAX: 610-765-1264


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