Report Examines Imaging Approach With Potential to Detect Lung Cancer at the Cellular Level

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Researchers have found a way to identify lung cancer at the cellular level in real time during a biopsy, which may enable detection of the disease earlier and with more confidence. The findings, published by Kennedy et al in Nature Communications, demonstrated that an imaging agent detected via guided technology during biopsies in real time can effectively light up cancer cells that may have been too small to detect using existing technology. Based on the more easily identifiable presence of fluorescent cancer cells generated by the new imaging approach, five nonexpert raters diagnosed malignant or nonmalignant tissue biopsies with 96% accuracy and made no false-negatives on the 20 human biopsy specimens they reviewed.

NIR-nCLE Method

The team examined cancer cells from patients who had a history of smoking. Researchers took the cancer cells and grew them with the normal cells in the laboratory to see how small a quantity of cell could be detected. Then, with an investigational imaging agent, pafolacianine injection, paired with Cellvizio, a probe- and needle-based imaging platform, they discovered that integrating the technologies allowed researchers to detect cancer at the cellular level in real time during biopsy in various preclinical models, including in culture, small animal models, and human tissue from patients undergoing surgery for lung cancer as part of an ongoing clinical trial. The researchers call the new technology NIR-nCLE, as it combines the cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system, which is modified to detect the NIR signal.

Biopsies of suspicious tissue are not always effective, because many times the concerning nodules may be too small to see and to remove for further testing. Not only does this leave many patients and physicians uncertain about whether cancer is present, it requires the need for additional biopsies and radiologic surveillance until the nodule is big enough to see for removal and evaluation via a histopathologic evaluation, which can take several days to complete. Current medical technology does not provide real-time diagnostic information during biopsy.

Methods like NIR-nCLE, which aim to find these microscopic nodules, can offer greater precision in the identification and, later, removal of cancer cells.

Unique Approach

“The emerging ability to light up a single cell that may be invisible to the eye provides great opportunity to give patients the best chance at an early diagnosis before cancer spreads,” said first study author Gregory T. Kennedy, MD, a resident in General Surgery at the University of Pennsylvania School of Medicine. “This unique approach has the potential to improve the information we get from biopsies and it may increase our chances of identifying cancer early.”

“This research shines a light on the possibility of being able to more accurately identify and diagnose lesions that could be cancerous, even those that are very small and may evade our typical diagnostic capabilities,” said corresponding study author Sunil Singhal, MD, Chief of the Division of Thoracic Surgery, the William Maul Measey Associate Professor in Surgical Research, and Director of the Center for Precision Surgery at the Abramson Cancer Center at the University of Pennsylvania School of Medicine. “The quest to diagnose lung cancer in earlier stages is a centerpiece of our research, since early detection is so closely connected to chances for successful treatment.”

Disclosure: This study was funded by the National Cancer Institute, the American Philosophical Society Daland Fellowship in Clinical Investigation, a Thoracic Surgery Foundation Resident Research Scholarship, and the Pennsylvania Health Research Formula Fund. For full disclosures of the study authors, visit

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