Cathepsin detection to identify malignant cells during robotic pulmonary resection

Area of Science:

• Oncology
• Surgical Innovation
• Medical Imaging

Background:

• Intraoperative molecular imaging (IMI) employs fluorescent probes to detect occult cancers.
• VGT-309 is an activity-based probe activated by cathepsins, enzymes often overexpressed in cancer cells.
• Near-infrared (NIR) light detects activated VGT-309, highlighting cancerous tissues.

Purpose of the Study:

• To evaluate the sensitivity and positive predictive value (PPV) of robotic-assisted thoracic surgery with intraoperative molecular imaging (RIMI) using VGT-309.
• To assess RIMI's ability to localize tumors via NIR light detection of cathepsin activity.
• To compare RIMI with video-assisted thoracic surgery combined with intraoperative molecular imaging (VIMI).

Main Methods:

• A phase 2 clinical trial involved 10 patients with suspicious pulmonary lesions undergoing robotic-assisted thoracic surgery (RATS).
• Procedures involved initial white light visualization followed by RIMI to identify cathepsin activity.
• VIMI was performed subsequently to compare diagnostic performance; resected specimens underwent fluorescence evaluation and histopathological analysis.

Main Results:

• RATS with white light identified 6/10 nodules; RIMI identified an additional 4 nodules, increasing detection to 10/10.
• Both RIMI and VIMI detected 80% of nodules, showing clinical equivalence.
• RIMI and VIMI sensitivity was 88.9%, superior to RATS alone (55.6%); PPV was 100% for RIMI/VIMI versus 83.3% for RATS.

Conclusions:

• RIMI using VGT-309 is effective for visualizing occult disease by detecting cathepsin activity.
• In this series, RIMI and VIMI demonstrated comparable sensitivity and PPV for identifying cathepsin activity.
• RIMI enhances tumor localization in thoracic surgery, potentially improving patient outcomes.