Military intelligence enables us to prepare for untoward events, improving our chances of curbing them. Likewise, “medical intelligence” – the early diagnosis of diseases, including cancer – can buy information and time, crucial factors that can significantly increase chances of recovery. For this reason, scientists all over the world are striving to develop advanced methods for the early diagnosis of cancer.
Prostate cancer is the second most common lethal cancer in men over 60, claiming a quarter of a million lives worldwide each year. There is a need for new methods that can provide reliable and sensitive early detection. Currently, recommended screening for prostate cancer is based on a combination of digital rectal examination, ultrasound and testing the amount of a prostate protein, PSA, in the blood. But these methods are neither sensitive nor reliable enough: Often the tests fail to sound the alarm bells, leaving the cancer to grow undetected, while in a considerable number of cases the tests set off false alarms, flagging benign and non-malignant conditions as potentially cancerous. In addition, these screening tests do not provide information about the exact size or location of the tumor and, worse, they are unable to determine the aggressiveness or clinical stage of the tumor. As a result, many older men are referred for biopsies, which, in as many as three out of four cases, prove negative (though even biopsies can produce false negatives). Because a biopsy is a painful and costly procedure, many scientists worldwide are searching for a non-invasive alternative.
Prof. Amos Breskin and Dr. Rachel Chechik, together with Dr. Sana Shilstein and research student Marco Cortesi of the Weizmann Institute’s Particle Physics and Astrophysics Department, in collaboration with Dr. David Vartsky of Soreq NRC, have recently developed a new concept for prostate cancer diagnosis. The method, which begins by detecting prostate zinc levels with X rays, is presently being tested in clinical trials in collaboration with Prof. Jacob Ramon and Drs. Eduard Fridman, Gil Raviv, Alexander Volkov and Nir Kleinman of Sheba Medical Center, Tel Hashomer; as well as Drs. Evyatar Moriel, Monica Huszar, Gabriel Kogan and Valery Gladysh of Kaplan Medical Center, Rehovot.
The method derives from three-decade-old observations that the concentration of zinc – an element found naturally and abundantly in healthy prostatic tissue – is low in the prostates of men suffering from advanced prostate cancer. The last decade has brought further insight into the role of zinc in the prostate; it’s involved, among other things, in the secretion of citrate-rich prostatic fluid.
The research team wanted to know whether a prostate zinc deficiency could be identified in earlier stages of cancer. They performed a clinical study on about 600 patients who had been referred for biopsies. They then measured the concentration of zinc in the biopsy samples using X-ray-based elemental analysis and compared the results with zinc levels in the blood. The results, which were published in The Prostate, not only showed that lowered levels of zinc in malignant prostate tissue could be detected at very early stages of the disease, they also showed, for the first time, that zinc depletion is positively correlated with tumor aggressiveness: The more aggressive the tumor, the greater the zinc depletion. In contrast, the benign tissue surrounding the tumor contained normal zinc levels. These three findings imply that mapping zinc in the prostate might be a useful way of pinpointing the exact location of a tumor and gauging its aggressiveness.
In a subsequent study, published in Physics in Medicine and Biology, the researchers tested whether images of prostatic zinc concentrations could potentially be used in a non-invasive X-ray-screening method. The method was assessed on the basis of computer-simulated images, using zinc concentration values obtained from the clinical trials. By analyzing the images and revealing the regions of depleted zinc, the researchers could not only classify an area as cancerous or benign but also determine the aggressiveness of the cancer as well as its dimensions and location within the prostate gland.
On the basis of these results, the team has launched an R&D program to promote the development of a non-invasive, transrectal probe that will generate zinc maps of the prostate gland through X-ray imaging.
Chechik: “Although it’s a few years away from production, we hope that the probe will be able to grade the aggressiveness of the tumor as well as indicate whether the cancer might have proliferated to areas outside the prostate gland. This information will help physicians decide whether a biopsy should be performed and significantly increase the sensitivity and accuracy of the biopsy.” Breskin: “The method is designed to help, in the future, in clinical decision making, as well as to be used to guide focal treatments. At the post-treatment stage, the probe could be an effective, non-invasive follow-up tool.”
Prof. Amos Breskin’s research is supported by the Helen and Martin Kimmel Center for Archaeological Science. Prof. Breskin is the incumbent of the Walter P. Reuther Chair of Research in Peaceful Uses of Atomic Energy.