A reliable, low-cost means of early detection of cancer would be of great benefit. Approaches to the treatment are advancing to the point at which very early stage cancer has a high rate of survival, and the side-effects of treatments for early stage cancer are becoming less onerous. In the ideal world, a yearly physical would include a low-cost cancer screen that robustly detects even small volumes of cancerous tissue. Various approaches are under development, such as those based on identification of signal molecules in the bloodstream. The alternative approach noted here, based on the use of engineered nanoparticles, is an interesting one, as it can in principle also be used to locate a cancer following the initial low cost screening.
Researchers have been developing cancer diagnostics that work by generating synthetic biomarkers that can be easily detected in the urine. Most cancer cells express enzymes called proteases, which help them escape their original locations by cutting through proteins of the extracellular matrix. Cancer-detecting nanoparticles are coated with peptides that are cleaved by these proteases. When these particles encounter a tumor, the peptides are cleaved and excreted in the urine, where they can be easily detected. In animal models of lung cancer, these biomarkers can detect the presence of tumors early on; however, they don't reveal the exact location of the tumor or whether the tumor has spread beyond its organ of origin.
Building on their previous efforts,researchers wanted to develop what they call a "multimodal" diagnostic, which can perform both molecular screening (detecting the urinary signal) and imaging, to tell them exactly where the original tumor and any metastases are located. To modify the particles so they could also be used for PET imaging, the researchers added a radioactive tracer. They also coated them with a peptide that is attracted to acidic environments, such as the microenvironment in tumors, to induce the particles to accumulate at tumor sites. Once they reach a tumor, these peptides insert themselves into cell membranes, creating a strong imaging signal above background noise.
The researchers tested the diagnostic particles in two mouse models of metastatic colon cancer, in which tumor cells travel to and grow in the liver or the lungs. After treatment with a chemotherapy drug commonly used to treat colon cancer, the researchers were able to use both the urine signal and the imaging agent to track how the tumors responded to treatment. This kind of diagnostic could be useful for evaluating how well patients respond to treatment, and for long-term monitoring of tumor recurrence or metastasis, especially for colon cancer. In the longer term, researchers hope that this technology could be used as part of a diagnostic workflow that could be given periodically to detect any kind of cancer.