The early detection of cancer directly affects the chances of survival for the patient. Thus, the tests and imaging currently available can be a matter of life and death for some patients. More often than not, blood or urine tests can detect cancer but not provide the direct location of any tumors present. Similarly, imaging techniques, including x-ray, can give the location of larger tumors but often miss those smaller in size. Hence, researchers in this field are working towards a hybrid version consisting of these two tests. To this end, researchers at the Massachusetts Institute of Technology (MIT) have engineered a test that can detect cancer cells in urine and locate any tumors in what’s known as a ‘multimodal’ test.
Early diagnosis of cancer focuses on identifying the disease using screening techniques as early as possible. To avoid delays in cancer care that could lower the chance of survival, cause more problems with treatment, or raise care costs. A doctor may investigate the patient’s personal and family medical history and perform a physical exam when screening for cancer. Dependent on the outcome, the clinician may also order lab or imaging tests which may need to be verified using a tissue biopsy.
Many tests doctors use to diagnose cancer — such as mammography, colonoscopy, and CT scans — are based on imaging. But recently, researchers have also developed lab tests that can detect specific cancer-associated molecules that circulate in bodily fluids like blood or urine. However, these all possess limitations, with no single test able to provide a complete diagnosis when used independently.
Now, a study from MIT engineers develops a new diagnostic nanoparticle that combines imaging with lab tests in a single multimodal test. That can ascertain the presence of cancer markers through a urine test and function as an imaging agent to pinpoint the tumor location. The team hopes oncology teams could use their diagnostic to identify and locate cancer anywhere in the body, including metastasized tumors at multiple sites. The study is published in the journal Nature Materials.
Previous studies show that imaging tests can uncover large clusters of cancer cells, yet they can’t capture a single cancer cell – meaning millions of cells are needed to make a tumor large enough to show up on a scan. Accordingly, treatment may continue even when small groups of cancer cells are no longer showing up on imaging tests. On the other hand, imaging tests sometimes show something like cancer, but further tests (like a biopsy) show that it’s not cancer.
Recent studies from the group developed diagnostics that cause cancer cells to generate synthetic biomarkers in urine. Cancer cells express enzymes known as proteases, which enable them to metastasize by cutting through the cell surface and the surrounding environment. A peptide used to coat the nanoparticles reacted with these enzymes, causing the proteases to leach out of the cancer cells into the urine, where the medical team could detect them.
However, even though these nanoparticles could identify cancer on a single cell basis, they could not reveal the exact location of the tumors.
The current study develops a “multimodal” diagnostic, which can identify cancer cells in urine and produce images detailing the position of tumors metastasized in the body.
Firstly, the lab had to modify the particles for use in PET imaging. To do this, they added a radioactive tracer called copper-64 and coated the nanoparticles with a peptide attracted to the acidic environment of tumors to induce the particles to accumulate at tumor sites. Once they reach a tumor, these peptides insert themselves into cancer cells, creating a solid imaging signal enabled by the copper-64.
The researchers trialed the diagnostic particles in two mouse models of metastatic colon cancer, where tumor cells invade the liver or the lungs. After treatment with a commonly used chemotherapy drug, the novel multimodal imaging tracked how the tumors responded to the chemo.
Amazingly, the hybrid nanoparticle not only monitored the progression of colon cancer but also captured the metastasis of tumors to the lung and the liver.
Eventually, the team hopes their technology could be performed regularly as part of routine cancer care. “The vision is that you could use this in a screening paradigm — alone or in conjunction with other tests — and we could collectively reach patients that do not have access to costly screening infrastructure today,” she says. “Every year, you could get a urine test as part of a general check-up. You would do an imaging study only if the urine test turns positive to determine where the signal is coming from. We have a lot more work to do on the science to get there, but that’s where we would like to go in the long run.”
For the future, the researchers envision that this diagnostic could help evaluate how well patients respond to treatment and monitor tumor recurrence or metastasis over an extended period, particularly in colon cancer.
Image courtesy of Massachusetts Institute of Technology (MIT)
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