Boston researchers have developed an implantable device that could help doctors monitor whether chemotherapy drugs are reaching tumors. The device could also rapidly verify whether the drugs are working and alert the doctors if the cancer recurs. The tiny silicone rod holds nanoparticles designed to clump and become visible on an MRI scan in the presence of cancer markers such as growth hormones and cancer drugs. The device, which is in preclinical tests in mice, can be implanted in inoperable tumors during a routine biopsy.
Today, the only way to tell whether a cancer drug is working is to monitor changes in tumor size over the course of months. Led by Michael Cima, MIT professor of materials science and engineering, the researchers hope their implant will help doctors monitor cancer patients in real time. Current monitoring timescales are “too long,” says Linda Molnar, consultant program officer at the National Cancer Institute’s Center for Strategic Scientific Initiatives. “You don’t know if a very toxic treatment is helping,” she says. Cima’s real-time monitoring device could be “an enabling technology for personalized medicine.”
The trend in cancer-drug development is toward multiple drugs with specific molecular targets. Faced with so many treatment options, Cima says, doctors will need to assess a drug’s effects much more quickly.
Cima’s tumor monitor is a silicone rod about eight microliters in volume filled with sensing nanoparticles. At the center of each particle is iron oxide, a good contrast agent for MRI scans. However, because the particles are so small, it’s only when they clump together that they are easy to see on an MRI scan. The iron-oxide particles are coated with the carbohydrate dextran, to which the researchers can attach multiple antibodies for whatever molecule in the tumor environment they want the device to detect. When the target molecule enters the device, several nanoparticles will attach to it and become visible as a dark speck on an MRI scan.
The implant has a semipermeable membrane whose pores are too small to let out the nanoparticles but large enough to let in drug molecules and proteins. The introduction into the body of antibodies like those on the nanoparticles can cause dramatic and unpredictable immune responses. But if his device works correctly, says Cima, all the nanoparticles will stay in the rod.
The silicone rod is small enough to be implanted during a traditional needle biopsy. “It’s no more invasive than what’s done already [in a biopsy],” Cima says. Many kinds of tumors–especially in the brain, head, and neck–can’t be removed surgically because of their location or because they are so diffuse. In such cases, doctors can only provide chemotherapy and hope the tumor shrinks. Cima’s device could help them monitor treatment of these inoperable tumors.
Cima says his group can design the nanoparticles to detect almost anything by choosing the right antibody. He and his colleagues are currently testing implants that can detect one molecule, the hormone hCG (which is made by several tumors), in mice. Cima’s MIT lab is working with that of Ralph Weissleder, director of Harvard University’s Center for Molecular Imaging Research, to develop the nanoparticles. Other collaborators include MIT professor Robert Langer, who is a leader in nanomedicine.
Cima is also developing tumor implants with multiple chambers, each of which holds nanoparticles that can detect a different molecule. (The nanoparticles can’t be combined in the same chamber because they can’t be distinguished in an MRI scan unless they are in spatially distinct locations.) Such devices could be read again and again over the course of a patient’s treatment; each chamber would show up as a different spot on an MRI image. Particles in one chamber might detect the presence of a drug in the tumor. Those in another chamber might detect a product of cancer metabolism like glucose, which would help doctors monitor the effects of a drug on a tumor’s activity. Once their tumors have shrunk, patients harboring the implant could be monitored for signs that the cancer has come back.
Looking to the future, Cima says he hopes the process won’t involve running patients through an MRI scanner again and again. His group is working to modify a portable MRI machine to function with the detecting implant. About the size of a box of tissues, the scanner could be waved over the part of the body that harbors the device and take a quick image.
Molnar says the monitoring implant could provide peace of mind for patients. “The earlier you detect [cancer recurrence], the easier it is to treat,” she says.
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