Winship researchers and collaborators find a new MRI approach made cancer more visible in animal models, including small lesions missed by CT.
A new MRI approach made tiny lung tumors and early signs of cancer spread more visible in animal models, including several small lesions that CT scans failed to detect, according to research published in Science Advances.
The approach uses a specialized MRI contrast agent that attaches to collagen, a protein that can accumulate and become reorganized around invasive tumors. When the agent binds to collagen, it makes those areas appear more clearly on MRI.
The findings suggest that the technology could one day help physicians detect lung cancer and metastases earlier while also providing clues about how invasive a tumor may be. (The research is preclinical, and the contrast agent has not yet been tested or approved for use in patients.)
Jenny J. Yang, PhD, and Wei Zhou, PhD
The study was co-led by Wei Zhou, PhD, professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and co-leader of the Cell and Molecular Biology Research Program at Winship Cancer Institute of Emory University, and Jenny J. Yang, PhD, who was at Georgia State University when this work was conducted and has since become professor and Presidential Faculty Scholar in the Division of Hematology and Oncology at the University of Alabama at Birmingham.
“This breakthrough was made possible through a close collaboration between Georgia State University and Emory University, bringing together complementary expertise in advanced imaging and cancer biology,” says Zhou, a co-corresponding author of the study.
Yang led the Georgia State University team that developed the collagen-targeted contrast agent before joining UAB. At Emory, Yijian Fan, working in Zhou’s laboratory, developed specialized models that closely reproduce how lung cancer can spread to other organs.
“By combining these innovative technologies and models, we were able to visualize invasive lung cancer and its spread to distant organs at much earlier stages than previously possible,” Zhou says.
Making cancer easier to see
CT is widely used to detect and monitor lung cancer, but very small tumors and metastases in soft tissues can be difficult to identify. MRI provides detailed images without exposing patients to ionizing radiation, but conventional MRI contrast agents are not designed to recognize specific features within and around tumors.
The researchers developed an experimental contrast agent, known as hProCA32.Collagen, that targets collagen I. Collagen ordinarily provides structure and support throughout the body, but its amount and organization can change within the environment surrounding a tumor as cancer becomes more invasive.
The researchers first examined tissue samples from 15 people with lung adenocarcinoma and confirmed increased collagen around the tumors and within the surrounding tissue. They then evaluated the imaging approach in several mouse models of primary and metastatic lung cancer.
In one model, the collagen-targeted MRI approach detected all 18 lung nodules later confirmed through tissue analysis, including lesions measuring less than 1 millimeter. CT missed several of the smallest nodules.
In another model, the MRI approach detected cancer in the lungs as well as very small metastases in the adrenal glands and kidneys. CT did not detect the adrenal and kidney metastases identified through the collagen-targeted MRI and subsequent tissue analysis.
The researchers confirmed the imaging results by examining the tissues after the scans. Tumor measurements obtained through MRI also closely matched those found through tissue analysis.
By combining several types of MRI images, the researchers were able to see the tumors more clearly than with CT or MRI using a conventional contrast agent. The experimental agent also helped reveal differences in the amount of collagen within and around individual tumors.
Identifying signs of invasive cancer
The study focused in part on lung adenocarcinomas with changes to a tumor suppressor gene known as LKB1 or STK11. These cancers can be aggressive and difficult to treat.
Previous research from the Emory group showed that loss of LKB1 can change the organization of collagen around a tumor, particularly at the edges where cancer cells are invading surrounding tissue. In the new study, areas with more collagen at the invasive tumor edge produced stronger MRI signals.
This finding suggests that the approach could potentially provide information not only about the location of cancer but also about whether a tumor has features associated with invasion and metastatic spread.
“The findings highlight the potential of advanced MRI technology to provide earlier and more precise information about cancer progression,” Zhou says.
If future studies establish that the approach is safe and effective in people, it could have potential applications in diagnosing and staging cancer, monitoring changes over time and evaluating how tumors respond to treatment.
Moving toward clinical study
The findings remain an early step toward possible clinical use. Although the researchers examined human lung cancer tissues to confirm collagen expression, the imaging agent itself has been evaluated only in preclinical models.
Additional safety studies and regulatory review will be required before it can be tested in patients. The research team has met with the U.S. Food and Drug Administration to discuss a proposed clinical trial design and possible pathways for moving the technology toward human testing.
Future research may also examine whether different targeted MRI agents could be combined to reveal more about the biological differences within and among tumors. That possibility was not tested in the current study.
Dongjun Li, PhD, and Oluwabukola Bamishaye, PhD, are co-first authors of the study. Zhou and Yang are co-corresponding authors. Other Emory-affiliated authors include Sandi Li, Xuxin Chen, Yijian Fan, PhD, Xiaofeng Yang, PhD, Alton B. Farris III, MD, Hua Yang, Jennifer W. Carlisle, MD, Suresh S. Ramalingam, MD, and Hans E. Grossniklaus, MD, MBA. The research was supported in part by two National Cancer Institute grants to Zhou, the Emory Lung Cancer Program Project grant and Winship’s NCI Cancer Center Support Grant, along with additional National Institutes of Health funding and Georgia State University fellowships.
The published study discloses that Yang holds shares in InLighta BioSciences, which licenses rights to commercialize the protein contrast agents, and is an inventor on related patents. The other authors report no competing interests.