Researchers at the Abramson Cancer Center at the University of Pennsylvania have developed a method to detect lung cancer at the cellular level in real time during biopsy. The method ensures earlier detection of 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 technology, five nonexpert raters diagnosed the malignant or nonmalignant tissue biopsies with 96% accuracy and made no false negatives on the 20 human biopsy specimens they reviewed. Scan of a patient in the Penn Medicine-led study with a lung nodule, circled in red. Courtesy of Penn Medicine. The researchers examined human cancer cells from patients with a history of smoking. The cancer cells were grown with the normal cells in the laboratory to see how small a quantity of cell could be detected. With an investigational imaging agent, Cytalux (pafolacianine) injection, paired with Cellvizio, a probe and needle-based imaging platform, the researchers discovered that integrating the technologies allowed them 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; many times the concerning nodules may be too small to see and to remove for further testing. This causes uncertainty in many patients and physicians about whether cancer is present, and requires the need for additional biopsies and radiological surveillance until the nodule is big enough to see for removal and evaluation via a histopathologic evaluation. This process can take several days to complete. Further, current medical technology does not provide real-time diagnostic information during biopsy. “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 Gregory Kennedy, a resident in general surgery at Penn. “This unique approach has the potential to improve the information we get from biopsies and it may increase our chances of identifying cancer early.” Methods like NIR-nCLE, which aim to find these microscopic nodules, can offer greater precision in the identification and, later, removal of cancer cells. “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 Sunil Singhal, 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. “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.” The researchers hope this approach can be used to help with earlier diagnosis of other cancer types. The U.S. Food and Drug Administration recently approved Cytalux for use in adult patients with ovarian cancer as an add-on during surgery to identify cancerous lesions. 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. The research was published in Nature Communications (www.doi.org/10.1038/s41467-022-30265-z).