Researchers at the University of Pennsylvania’s Abramson Cancer Center have discovered a mechanism to detect lung cancer at the cellular level in real-time during a biopsy, indicating that the disease can be detected earlier and with greater confidence.
The findings, which expand on prior Penn research, show that an imaging agent discovered in real-time during biopsies using guided technology can efficiently light up cancer cells that were previously too small to identify with current equipment.
Five non-expert raters diagnosed malignant or non-malignant tissue biopsies with 96 percent accuracy and no false negatives on the 20 human biopsy specimens they assessed, based on the more easily recognizable presence of fluorescent cancer cells generated by the new imaging approach. The findings were published in Nature Communications this week.
Human cancer cells from people with a history of smoking were investigated by the Penn researchers. In the laboratory, researchers cultured cancer cells alongside normal cells to examine how small a number of cell might be detected.
The researchers then discovered that combining CytaluxTM (pafolacianine) injection with Cellvizio®, a probe and needle-based imaging platform, allowed them to detect cancer at the cellular level in real time during biopsy in a variety of preclinical models, including culture, small animal models, and human tissue from patients undergoing lung cancer surgery as part of an ongoing clinical trial.
The NIR-nCLE method combines a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) device that has been adapted to detect the NIR signal, according to the researchers.
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.
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.
Sunil Singhal
Not only does this leave many patients and doctors unsure if cancer is present, but it also necessitates additional biopsies and radiological surveillance until the nodule is large enough to remove and evaluate via a histopathologic assessment, which can take several days.
During a biopsy, current medical equipment does not provide real-time diagnostic information. Methods like NIR-nCLE, which aim to locate these minute nodules, can improve the precision with which cancer cells are identified and then removed.
“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 T. Kennedy, MD,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.”
Lung cancer is the third most frequent cancer in the United States, according to the Centers for Disease Control and Prevention (CDC), and it kills more men and women than any other variety. Every year, more than 236,000 people are diagnosed with the disease, and more than 130,000 people die from it.
“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, 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 Penn.
“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 that this method can be utilized to aid in the early detection of additional cancer forms. Additional targeted imaging methods for lung, brain, breast, sarcoma, head and neck, and urinary tract malignancies have been developed by Penn researchers and industry partners.
Cytalux was recently licensed by the US Food and Drug Administration (FDA) for use in adult patients with ovarian cancer as an add-on during surgery to identify malignant tumors.
Since its creation in 2015, the Center for Precision Surgery and its half-dozen affiliated labs have created a number of new focused imaging technologies. To far, more than 1,200 patients have participated in clinical investigations conducted by Penn physicians and researchers.
Cytalux, a drug developed by On Target Laboratories, was found in the latest study using Mauna Kea Technologies’ Cellvizio®, a real-time in vivo cellular imaging technology.
The National Cancer Institute (F32 CA254210-01, R01 CA193556), the American Philosophical Society Daland Fellowship in Clinical Investigation, a Thoracic Surgery Foundation Resident Research Scholarship, and the Pennsylvania Health Research Formula Fund all contributed to this research.
