Intraoperative Molecular Imaging in Thoracic Oncology: Expanding the Observable Disease Space
Eliana Marostica1, Sunil Singhal1
1Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Background/Objectives:
Intraoperative molecular imaging (IMI) enables real-time visualization of tumor biology during surgery using fluorescent probes and near-infrared imaging systems. As lung cancer screening increases detection of small and nonpalpable pulmonary nodules, conventional localization and margin assessment techniques remain limited, particularly during minimally invasive surgery. This review summarizes the technical foundations, imaging agents, clinical applications, and future directions of IMI in thoracic oncology.
Methods:
We performed a narrative review to synthesize current evidence regarding the technical foundations, molecular imaging agents, clinical applications, and future directions of intraoperative molecular imaging in thoracic oncology. Given the multidisciplinary scope of the field, a narrative approach was selected to integrate mechanistic, translational, and clinical evidence rather than to answer a single narrowly defined clinical question.
Results:
IMI generates dynamic intraoperative contrast based on preferential probe accumulation or activation within malignant tissue. Current approaches include non-specific fluorophores such as indocyanine green, activatable probes targeting tumor-associated proteases or acidic microenvironments, and receptor-targeted agents such as pafolacianine. Across prospective studies and multicenter trials, IMI improved localization of nonpalpable lesions, identified occult synchronous malignancies, and enhanced intraoperative margin assessment, frequently altering surgical management. Phase 2 and 3 studies of folate receptor-targeted imaging demonstrated clinically significant findings in a substantial proportion of patients, including lesions not detected by conventional imaging or palpation. However, performance remains dependent on tumor biology, target expression, lesion depth, and optical constraints.
Conclusions:
IMI represents an emerging transition from anatomy-guided toward biology-informed thoracic surgery by providing real-time molecular information during resection. Current evidence supports its role as a complementary intraoperative technology that augments conventional imaging and surgical techniques, particularly for small, peripheral, and nonpalpable lesions.
Insights
Intraoperative molecular imaging (IMI) enhances thoracic surgery by visualizing tumor biology in real-time. This technology improves the detection and margin assessment of small lung nodules, guiding surgeons with molecular insights.
Area of Science:
- Oncology
- Surgical Technology
- Medical Imaging
Background:
- Lung cancer screening detects more small, nonpalpable nodules.
- Conventional methods struggle with localization and margin assessment in minimally invasive thoracic surgery.
- Intraoperative molecular imaging (IMI) offers real-time visualization of tumor biology.
Purpose of the Study:
- To review the technical aspects, imaging agents, clinical uses, and future of IMI in thoracic oncology.
- To synthesize evidence on IMI's role in improving surgical outcomes for lung cancer.
- To highlight IMI's potential to shift thoracic surgery towards biology-informed approaches.
Main Methods:
- A narrative review was conducted.
- Evidence was synthesized from mechanistic, translational, and clinical studies.
- Focus was on technical foundations, imaging agents, clinical applications, and future directions of IMI.
Main Results:
- IMI uses fluorescent probes and near-infrared systems for real-time visualization.
- Approaches include non-specific fluorophores, activatable probes, and receptor-targeted agents.
- IMI improved localization, identified occult malignancies, and enhanced margin assessment, altering surgical management in trials.
Conclusions:
- IMI provides real-time molecular information, transitioning thoracic surgery to a biology-informed approach.
- Current evidence supports IMI as a complementary tool augmenting conventional techniques.
- IMI is particularly beneficial for small, peripheral, and nonpalpable lesions in thoracic oncology.
