Abstract
Implanted into cancerous tissue during a biopsy, a new biochemical sensor, currently tested in small animals, could tell doctors how well a patient's treatment is working in a matter of days.
To determine if a cancer therapy is working, physicians often use MRI to gauge tumor size. However, it can take weeks or months to see MRI evidence of tissue loss or disease progression. Now, researchers have built a tiny biochemical sensor that a doctor could implant during biopsy to measure local changes in pH and dissolved oxygen. Described in a recent paper, the device has been tested in vitro and in rodents (Lab Chip 2015;15:3465–72). If it works in patients, the data it collects could help determine—within a few days—whether a tumor is responding to a given therapy.
MRI requires the use of contrast agents to enhance structures or fluids in the body. Visualizing a pea- or walnut-sized tumor should require only “a tiny amount of contrast agent,” says Christophoros Vassiliou, PhD. However, these agents rapidly disperse throughout the body. Vassiliou is a postdoc at the University of California, Berkeley, who previously worked with the study's senior author, Michael Cima, PhD, of MIT's Koch Institute for Integrative Cancer Research in Cambridge.
Rather than inject a typical MRI contrast agent, Vassiliou and co-author Vincent Liu, PhD, wondered, “Could we drop in a sensor?”
To explore that question, several years ago the researchers built an injectable oxygen sensor by enclosing a contrast agent within a polymeric matrix (Proc Natl Acad Sci 2014;111:6588–93). Although the system prevented dispersion of the contrast agent, it still required MRI—a costly, specialized procedure—to distinguish signals coming from the contrast agent from those of the surrounding tissue.
Now, to resolve that problem, the researchers incorporated electronics into the implanted sensor so it could measure local changes in oxygen concentration or pH without an MRI scanner. Instead, signals from the implanted sensor, which measures about 2 mm wide by 6 mm long, are detected by an external reader coil.
The team first tested its sensor in vitro in solutions with a known pH, as well as in gas flow tubes where oxygen concentration could be controlled. In vivo, the sensor measured pH when placed into a xenograft tumor model in mice and sensed changes in dissolved oxygen when implanted into the calf muscle of a rat subjected to ischemia by constricting the hind leg.
The system is not yet ready to be tested in larger organisms. Detecting signals from the sensor implanted deep inside a human patient would require an external reader with larger magnets than in the current design, says Vassiliou.
Researchers have developed a biochemical sensor about the size of a pencil tip that could be implanted during a biopsy to measure local physiologic changes.
Researchers have developed a biochemical sensor about the size of a pencil tip that could be implanted during a biopsy to measure local physiologic changes.
In addition to tracking chemical changes within tumors, the sensor might identify rare cells or small amounts of viruses that escape detection with conventional methods involving PCR on blood samples. The sensor could potentially boost detectability by a factor of 100,000, suggests Sebastian Flacke, MD, PhD, chief of interventional radiology at Lahey Hospital & Medical Center in Burlington, MA. Letting the implant sit in the body for 10 minutes would expose the sensor to 40 L of blood instead of the mere 10 mL in a typical blood draw, Flacke notes.
For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
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