August 8, 2017

Contrast agent helps surgeons spot cancerous lung nodules

At a Glance

  • A new method improves the detection of cancerous lung nodules during surgery.
  • If validated in larger studies, the technique could help surgeons detect and more effectively remove cancer from the lungs. 
Surgeon holding a patient’s hands as they prepare for surgery. Researchers have been looking for ways to use tumor markers—substances produced at much higher levels in cancerous conditions—to improve cancer surgeries.XiXinXing/iStock/Thinkstock

Imaging tests such as CT and PET scans can detect growths, or nodules, in the lung. These nodules sometimes turn out to be cancer. The most accurate way to know whether or not a nodule is cancer is to remove and inspect the tissue by microscope to check for cancer cells. If the nodule is cancer, it may be lung cancer or another type of cancer that has spread to the lung.

Some imaging tests use contrast agents to make the tumor more obvious against healthy tissue. A new contrast agent called OTL38 consists of folate, a B vitamin, labeled with a dye. Receptors for folate are found on most cells, but many types of cancer cells have unusually large numbers of folate receptors on their surfaces. After a patient receives an intravenous (IV) injection of OTL38, the contrast agent flows throughout the body and binds to folate receptors. When exposed to light of a certain wavelength, tissues with high levels of OTL38-labelled receptors glow with fluorescent light.

A research team led by Dr. Sunil Singhal of the Abramson Cancer Center at the University of Pennsylvania explored the use of OTL38 for detecting lung nodules during surgery. The study was supported in part by NIH’s National Cancer Institute (NCI). Preliminary results were published on July 25, 2017, in the Annals of Surgery.

Malignant pulmonary nodule glowing during surgery Researchers used a contrast agent called OTL38 to make malignant pulmonary nodules easier to spot.Abramson Cancer Center at the University of Pennsylvania

Before surgery, the 50 men and women taking part in the study were evaluated with CT and PET scans. The research team identified a total of 66 lung nodules in the patients.

All patients received the OTL38 contrast agent several hours before surgery. During surgery, OTL38 caused 60 of the 66 previously detected nodules to glow. OTL38 also enabled the detection of 9 additional nodules not found by PET.

The surgeons removed all 75 nodules and sent them to the pathology lab. Tests confirmed that 68 nodules were cancer. The PET scan had shown 50 of these 68 cancers as suspicious for cancer; OTL38 had shown 65 of the 68 cancers as suspicious for cancer.

For nodules larger than 1 cm, PET missed seven cancers, and OTL38 missed three cancers. Together, the PET and OTL38 imaging methods detected all 10 of these cancers, and the surgeons were able to remove them from the lungs.

OTL38 also helped identify tumors that the surgeons could not see with regular white light or feel during surgery. Of the 17 nodules measuring less than 1 cm, 15 were detected with OTL38 and verified to be cancer. The other two nodules were benign and not detected by OTL38. PET detected four of these 15 small cancers. With PET, one nodule it detected turned out to be benign.

“This shows the contrast agent is allowing us to remove more cancer from the patient than we would have with PET imaging alone,” Singhal says. A larger study with twice as many patients is now in progress.

 —by Geri Piazza

Related Links

References: Intraoperative Molecular Imaging Combined With Positron Emission Tomography Improves Surgical Management of Peripheral Malignant Pulmonary Nodules. Predina JD, Newton AD, Keating J, Barbosa EM Jr, Okusanya O, Xia L, Dunbar A, Connolly C, Baldassari MP, Mizelle J, Delikatny EJ, Kucharczuk JC, Deshpande C, Kularatne SA, Low P, Drebin J, Singhal S. Ann Surg. 2017 Jul 25. doi: 10.1097/SLA.0000000000002382. [Epub ahead of print]. PMID: 28746152.

Funding: NIH’s National Cancer Institute (NCI); American Philosophical Society; and Association for Academic Surgery Foundation.