Preclinical Study Shows MRI and Chemical Contrast Solution Combination Can Detect Breast Cancer Micrometastases
Researchers have shown that magnetic resonance imaging (MRI) can detect the earliest signs of breast cancer recurrence and fast-growing tumors through detecting micrometastases, 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 work was completed at Case Western Reserve University and was funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health. Their findings were published by Zhou et al in Nature Communications.
“MRI has a wide array of diagnostic applications, and shows promise in breast cancer detection and treatment monitoring,” said Richard Conroy, PhD, Director of the NIBIB Division of Applied Science and Technology. “The technique used by researchers in this study enables very early detection of metastatic spread, which would allow adaptation of treatment more quickly and, hopefully, lead to better outcomes in the future.”
“We showed with this technique that we can detect very tiny tumors of just a few hundred cells,” said Zheng-Rong Lu, PhD, M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve. Dr. Lu added that the study pushed imaging boundaries, revealing that smaller cancers can be detected with current clinical imaging modalities. “Our imaging technology has the potential to differentiate aggressive tumors from low-risk tumors. These are two things that potentially can make a big impact on clinical practice and the management of cancer.”
Micrometastases and Early Detection
One-third of patients diagnosed with breast cancer eventually develop metastases in distant organs. Breast cancer has a high rate of metastasis to the bone, lung, liver, lymph nodes, and 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 nor early cancer growth.
The earliest signs of cancer spread—micrometastases—are often too small to be detected with standard screening. Dr. Lu's team employed a biochemical approach (using a special chemical contrast solution) combined with MRI to detect molecular changes that signal micrometastases.
The contrast solution contains a peptide tagged with a minuscule magnet. They chose the peptide for its inclination to bind to protein matrix structures around cancer cells called fibrin-fibronectin complexes. 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 primary tumor sends signals to distant tissue and organs to prepare for metastasis,” Dr. Lu said. “By also binding with the magnetically tagged peptide, the biomarker is enhanced, generating enough signal for MRI detection of small, high-risk cancer and micrometastases.”
Study Details
The researchers tested the approach in mice into which they had introduced breast cancer cells. After a 2-week waiting period, the researchers injected the contrast solution and performed an MRI. The MRI imaging detected metastatic tumors, including micrometastases, in the lung, liver, lymph node, adrenal gland, bone, and brain 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 cryoimaging, along with MRI, the researchers verified that the MRI technique could detect micrometastases, even observing bone micrometastases that were less than 0.5 mm.
Prior to their study with this contrast agent, Dr. Lu's team had conducted studies to determine its 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 recurrence rates of some forms of breast cancer and the consequence of metastatic cancer make these efforts urgent and important,” said Dr. Lu, adding that his research team also hopes to advance the approach for prostate cancer detection. “We think this targeted approach holds great promise for earlier imaging of high-risk cancers in the clinic. It could also become useful as a noninvasive way to assess breast cancer treatment progress.”
Dr. Lu and David L. Wilson, PhD, are the corresponding authors for the Nature Communications article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
