Researchers have shown that magnetic resonance imaging (MRI) can detect the earliest signs of breast cancer recurrence and fast-growing tumors. Their approach detects micromestastases, breakaway tumor cells with the potential to develop into dangerous secondary breast cancer tumors elsewhere in the body. The approach may offer an improved way to detect early recurrence of breast cancer in women and men. The study was published in the journal Nature Communications.
One-third of patients diagnosed with breast cancer eventually develop metastases in distant organs, with an increased risk of death. Breast cancer has a high rate of metastasis to bone, lung, liver, lymph nodes, and the brain. Since small, early-stage cancers are the most responsive to drug treatments, screening is an important aspect of follow-up care for breast cancer patients, and early detection is critical in tailoring appropriate and effective therapeutic interventions. While multiple imaging techniques, including MRI, are currently used in breast cancer detection and clinical management, they are neither able to detect specific cancer types or early cancer growth.
The earliest signs of cancer spread are called micrometastases. As the name implies, they are often too small to be detected with standard screening. To detect micromestastases, the researchers used MRI imaging - which uses a magnetic field and radio waves to produce images - and combined it with a special chemical contrast solution.
The contrast solution that the team developed contains a short piece of protein, or peptide, tagged with a minuscule magnet. They chose the peptide - a chain of just five amino acids - for its inclination to bind to protein matrix structures around cancer cells, called fibrin-fibronectin complexes. More importantly, the fibronectin part of the complex is expressed during a cell's transition to cancer and plays a role in cell growth, migration and differentiation. Fibronectin is associated with high-risk breast cancer with poor prognosis.
The researchers collected images depicting metastases where breast cancer had spread beyond the original tumors. Metal molecules within the contrast solution are magnetized during the MRI process and enhance the image wherever the molecules of solution bind with the targeted protein.
The researchers tested the approach in mice into which they had introduced breast cancer cells. After a two-week waiting period, the researchers injected the contrast solution and performed MRI. The MRI imaging detected metastatic tumors, including micrometastases, in lung, liver, lymph node, adrenal gland, bone, and brains of the mice.
Analysis of images showed that the contrast used by the research team bound almost exclusively to the fibrin-fibronectin complexes, producing a strong and prolonged image enhancement of micrometastases and tumors compared with normal tissue. Using a microscopic imaging approach, called cryo-imaging, and MRI, the researchers verified that the MRI technique could detect micrometastases, even observing bone micrometastases that were less than 0.5mm - the diameter of a very fine pencil lead.
The researchers have also conducted studies to determine the contrast agent's clearance from the body after the imaging, which is essential for safe clinical use. Their testing showed that the agent is readily cleared from the body and has a low level of retention in tissues. Therefore, they expect it will be safe if ultimately developed for clinical use.
The team plans to complete safety testing of the imaging agent during the next three years. They will then pursue human trials with this approach. They also hopes to advance the approach for prostate cancer detection.
Based on material originally posted by NIH/National Institute of Biomedical Imaging & Bioengineering.