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A pH-Activatable Nanoprobe Labels Diverse Histologic Subtypes of Human Lung Cancer During Resection
Gregory Thomas Kennedy1, Feredun S Azari1, Ashley Chang1
1Department of Surgery, University of Pennsylvania School of Medicine, 3400 Civic Center Boulevard, 14th Floor, South Pavilion, Philadelphia, PA, 19104, USA.
Molecular Imaging and Biology
|September 11, 2023
Summary
Pegsitacianine, a pH-activatable nanoprobe, successfully labeled common lung cancers in humans. This advance in intraoperative molecular imaging aids surgeons in identifying and resecting lung tumors more effectively.
Area of Science:
- Oncology
- Medical Imaging
- Nanotechnology
Background:
- Intraoperative molecular imaging (IMI) enhances cancer surgery using targeted contrast agents.
- pH-activatable contrast agents are emerging tools, but their use in lung cancer was unexplored.
- Pegsitacianine (ONM-100), a pH-activatable nanoprobe, was investigated for lung cancer surgery.
Purpose of the Study:
- To evaluate pegsitacianine for intraoperative molecular imaging in lung cancer.
- To assess the clinical translation and feasibility of pegsitacianine for fluorescence-guided lung cancer resection.
Main Methods:
- In vitro characterization of pegsitacianine's pH-dependent fluorescence.
- Preclinical testing in murine models of lung adenocarcinoma and squamous cell carcinoma.
- Clinical evaluation in patients undergoing lung cancer surgery within a phase 2 trial.
Main Results:
- Pegsitacianine fluorescence activated below physiologic pH.
- The probe selectively labeled lung cancer xenografts in preclinical models (TBR > 2.0).
- Successful real-time localization of pulmonary adenocarcinoma and squamous cell carcinoma in human subjects (TBRs= 2.7 and 2.4).
Conclusions:
- Pegsitacianine is feasible for intraoperative molecular imaging in lung cancer.
- The probe effectively labels the two most common lung cancer histologic subtypes.
- This study demonstrates successful clinical translation for improved surgical management.
