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Updated: Aug 12, 2025
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
Carcinoembryonic Antigen-Related Cell Adhesion Molecule Type 5 Receptor-Targeted Fluorescent Intraoperative Molecular
Feredun Azari1, Ruben P J Meijer2, Gregory T Kennedy1
1Department of Thoracic Surgery, University of Pennsylvania, Philadelphia.
Importance:
Localization of subcentimeter ground glass opacities during minimally invasive thoracoscopic lung cancer resections is a significant challenge in thoracic oncology. Intraoperative molecular imaging has emerged as a potential solution, but the availability of suitable fluorescence agents is a limiting factor.
Objective:
To evaluate the suitability of SGM-101, a carcinoembryonic antigen-related cell adhesion molecule type 5 (CEACAM5) receptor-targeted near-infrared fluorochrome, for molecular imaging-guided lung cancer resections, because glycoprotein is expressed in more than 80% of adenocarcinomas.
Design, Setting, And Participants:
For this nonrandomized, proof-of-principal, phase 1 controlled trial, patients were divided into 2 groups between August 1, 2020, and January 31, 2022. Patients with known CEACAM5-positive gastrointestinal tumors suggestive of lung metastasis were selected as proof-of-principle positive controls. The investigative group included patients with lung nodules suggestive of primary lung malignant neoplasms. Patients 18 years or older without significant comorbidities that precluded surgical exploration with suspicious pulmonary nodules requiring surgical biopsy were included in the study.
Interventions:
SGM-101 (10 mg) was infused up to 5 days before index operation, and pulmonary nodules were imaged using a near-infrared camera system with a dedicated thoracoscope.
Main Outcomes And Measures:
SGM-101 localization to pulmonary nodules and its correlation with CEACAM5 glycoprotein expression by the tumor as quantified by tumor and normal pulmonary parenchymal fluorescence.
Results:
Ten patients (5 per group; 5 male and 5 female; median [IQR] age, 66 [58-69] years) with 14 total lesions (median [range] lesion size, 0.91 [0.90-2.00] cm) were enrolled in the study. In the control group of 4 patients (1 patient did not undergo surgical resection because of abnormal preoperative cardiac clearance findings that were not deemed related to SGM-101 infusion), the mean (SD) lesion size was 1.33 (0.48) cm, 2 patients had elevated serum CEA markers, and 2 patients had normal serum CEA levels. Of the 4 patients who underwent surgical intervention, those with 2+ and 3+ tissue CEACAM5 expression had excellent tumor fluorescence, with a mean (SD) tumor to background ratio of 3.11 (0.45). In the patient cohort, the mean (SD) lesion size was 0.68 (0.22) cm, and no elevations in serum CEA levels were found. Lack of SGM-101 fluorescence was associated with benign lesions and with lack of CEACAM5 staining.
Conclusions And Relevance:
This in-human proof-of-principle nonrandomized controlled trial demonstrated SGM-101 localization to CEACAM5-positive tumors with the detection of real-time near-infrared fluorescence in situ, ex vivo, and by immunofluorescence microscopy. These findings suggest that SGM-101 is a safe, receptor-specific, and feasible intraoperative molecular imaging fluorochrome that should be further evaluated in randomized clinical trials.
Trial Registration:
ClinicalTrials.gov identifier: NCT04315467.
Insights
This study shows SGM-101, a novel near-infrared fluorochrome, can safely and effectively identify carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)-positive lung tumors during surgery. This molecular imaging agent aids in precise tumor localization for lung cancer resections.
Area of Science:
- Thoracic Oncology
- Molecular Imaging
- Surgical Navigation
Background:
- Accurate localization of small lung nodules during surgery is challenging.
- Intraoperative molecular imaging offers a potential solution for improved tumor visualization.
- Limited availability of effective fluorescence agents hinders current intraoperative imaging.
Purpose of the Study:
- To assess the utility of SGM-101, a CEACAM5-targeted near-infrared (NIR) fluorochrome, for guiding lung cancer resections.
- To determine if SGM-101 can effectively image tumors expressing CEACAM5, a glycoprotein found in over 80% of adenocarcinomas.
Main Methods:
- A nonrandomized, proof-of-principle, Phase 1 controlled trial was conducted.
- Patients received SGM-101 intravenously up to 5 days before surgery.
- Pulmonary nodules were imaged using a NIR camera system with a thoracoscope.
Main Results:
- SGM-101 demonstrated clear fluorescence in CEACAM5-positive tumors, with a mean tumor-to-background ratio of 3.11.
- Fluorescence correlated with CEACAM5 expression levels in resected tissue.
- Lack of SGM-101 fluorescence was associated with benign lesions and absence of CEACAM5 staining.
Conclusions:
- SGM-101 successfully localized to CEACAM5-positive tumors in patients.
- The study confirmed SGM-101's safety, receptor specificity, and feasibility for intraoperative imaging.
- Further evaluation in randomized clinical trials is warranted to confirm these promising findings.
