Collagen-Targeted MRI Agent Spots Tiny Lung Tumors and Hidden Metastases in Preclinical Tests

A protein-based MRI contrast agent developed by a multi-institutional team led by Georgia State University can detect invasive lung cancer and metastatic disease at earlier stages than conventional imaging approaches, according to a study published in Science Advances. The agent, called hProCA32.Collagen, enabled researchers in preclinical studies to identify tumors and metastases as small as 1 millimeter while mapping biological features linked to tumor invasion and progression. The work was led by Jenny J. Yang, Regents’ Professor Emerita of Biochemistry and Biophysical Chemistry at Georgia State, and jointly directed with Wei Zhou of Emory University’s Winship Cancer Institute.

“Lung cancer is often diagnosed only after it has spread, when treatment options become more limited,” Yang said. “Our technology can detect tiny tumors and hidden metastases without exposing patients to radiation. It also helps reveal how aggressive a cancer may be and how likely it is to spread, potentially reducing the need for invasive biopsies.” Unlike standard CT and MRI scans that rely on anatomical changes, the new agent is designed to bind collagen type I, a structural protein found at elevated levels in aggressive lung tumors and metastatic lesions. By targeting this feature of the tumor microenvironment, the method aims to highlight cancerous tissue molecularly rather than waiting for masses to become large enough to see on conventional images.

The collagen-targeting strategy builds on a previously reported imaging agent from Yang’s team that targeted CXCR4, a cancer biomarker. Together, these agents represent what the researchers describe as a new generation of molecular imaging technology intended to enhance imaging and improve detection of cancerous cells at earlier stages of development. In the preclinical studies reported in Science Advances, hProCA32.Collagen allowed the team to detect and quantify small lung tumors and metastases in the lung, adrenal glands and kidneys, providing quantitative measurements alongside visual localization. The approach proved particularly effective in aggressive lung adenocarcinomas associated with certain mutations, which are frequently resistant to current therapies and prone to spreading to multiple organs.

The findings emerged from a collaboration among Georgia State University, Emory University, The University of Alabama at Birmingham and other partner institutions, supported in part by funding from the National Institutes of Health. Yang’s team at Georgia State, including co-first authors Dongjun “Darren” Li and Oluwabukola “Sophia” Bamishaye of the university’s Center for Diagnostics and Therapeutics and Molecular Basis of Disease programs, led development of the contrast agent and the precision MRI methodology, with imaging studies conducted at Georgia State’s Advanced Translational Imaging Facility. Researchers at Emory, including co-corresponding author Zhou, contributed cancer models and expertise in cancer biology and translational research, while collaborators at UAB provided imaging physics expertise and additional imaging analysis.

“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,” Zhou said. By combining the imaging technology with sophisticated models of cancer metastasis, the researchers were able to visualize invasive lung cancer and its spread to other organs at much earlier stages than previously possible in their experimental systems. Because the agent is protein-based and the imaging is MRI-based, the method avoids the ionizing radiation associated with CT scanning, a distinction the researchers emphasize for repeated monitoring over the course of disease.

Beyond diagnosis, the team argues the findings could have implications for personalized cancer treatment. Because the agent visualizes collagen remodeling throughout both primary and metastatic tumors, physicians may eventually be able to use the signal to identify high-risk patients, guide treatment selection and monitor response to therapy over time. “This is a game changer for cancer diagnosis and precision medicine,” Yang said. “For the first time, we’ve shown that precision MRI can detect tiny tumors and whole body metastases without using harmful radiation while also providing important clues about how aggressively a cancer may behave.”

Translation toward clinical use is being advanced by InLighta Biosciences, a biotechnology company founded by Yang that has licensed related intellectual property from Georgia State. Supported in part through NIH SBIR and STTR funding, the company is working to move next-generation protein-based diagnostic and therapeutic agents toward clinical development. The researchers are now also working toward an investigational new drug application with the U.S. Food and Drug Administration, the step required before the technology can begin testing in human clinical trials. Until such trials are completed, the reported detection capabilities remain established in preclinical cancer models rather than in patients, and the technology’s eventual performance in clinical screening and staging will need to be demonstrated under regulatory review.

Subject of Research: A collagen-targeted protein-based MRI contrast agent for early detection of invasive lung cancer and metastases

Article Title: New MRI agent detects lung cancer, hidden metastases earlier than current scans

Article References: New MRI agent detects lung cancer, hidden metastases earlier than current scans. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

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Keywords: MRI contrast agent, lung cancer, collagen type I, metastasis, molecular imaging, lung adenocarcinoma, tumor microenvironment, preclinical study, Science Advances, Georgia State University, early detection, precision medicine