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Updated: Jan 13, 2026
A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
Mitigating tumor heterogeneity in lung Cancer: A dual-targeted NIR-II imaging strategy for accurate tumor
Yifeng Li1, Chao Li2, Yueqi Wang3
1School of Engineering Medicine and School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, PR China; Key Laboratory of Big Data-Based Precision Medicine, Ministry of Industry and Information Technology, Beihang University, Beijing, 100191, PR China.
Abstract:
Precise localization and complete resection are critical for preventing recurrence in non-small cell lung cancer (NSCLC), yet these goals remain clinically challenging. The second near-infrared window (1000-1700 nm, NIR-II) fluorescent molecular imaging offers a promising solution, and single-targeted probes have been developed for intraoperative guidance. However, tumor heterogeneity often limits the efficacy of single-target antibody probes, resulting in low detection sensitivity. Therefore, this study aimed to evaluate a dual-targeting strategy simultaneously engaging EGFR and cMET for NIR-II-guided lung cancer surgery. Based on the higher overexpression of EGFR and cMET in NSCLC, we implemented the bispecific probe Amivantamab-IRDye800CW to establish a dual-targeting imaging strategy. After validating its superior properties and NIR-II imaging advantages, we assessed its tumor-targeting capability and surgical navigation potential through in vivo imaging. Additionally, freshly resected NSCLC specimens were incubated with probes to confirm target specificity. Amivantamab-IRDye800CW exhibited NIR-II fluorescence emission (up to 1500 nm), with improved imaging performance over NIR-I. In subcutaneous xenograft models, the probe demonstrated precise tumor targeting (tumor-to-background ratio = 6.79 ± 0.49) and enabled complete resection of both subcutaneous tumors and orthotopic lung tumors. The probe also retained strong targeting ability in patient-derived xenograft (PDX) models, which better preserve tumor heterogeneity. Furthermore, Amivantamab-IRDye800CW accurately localized cancerous tissues in clinical NSCLC specimens. These findings demonstrate that implementing a dual-targeting strategy in NSCLC, effectively reduces the impact of tumor heterogeneity on NIR-II imaging. This approach improves tumor localization precision and provides reliable intraoperative guidance, highlighting its strong potential for clinical translation in NSCLC surgery.
Insights
A novel dual-targeting imaging probe effectively guides non-small cell lung cancer (NSCLC) surgery by simultaneously targeting EGFR and cMET. This approach overcomes tumor heterogeneity, improving tumor localization and enabling complete resection for better patient outcomes.
Area of Science:
- Oncology
- Medical Imaging
- Molecular Probes
Background:
- Non-small cell lung cancer (NSCLC) recurrence is often linked to incomplete tumor resection.
- Current intraoperative guidance methods face challenges due to tumor heterogeneity.
- Near-infrared II (NIR-II) window fluorescence imaging shows promise for surgical guidance.
Purpose of the Study:
- To evaluate a dual-targeting strategy using Amivantamab-IRDye800CW for NIR-II-guided NSCLC surgery.
- To assess the probe's efficacy in overcoming tumor heterogeneity and improving detection sensitivity.
- To determine the probe's potential for precise tumor localization and complete resection.
Main Methods:
- Developed and validated a bispecific probe (Amivantamab-IRDye800CW) targeting EGFR and cMET.
- Assessed probe performance in vitro and in vivo using xenograft and patient-derived NSCLC models.
- Evaluated probe's fluorescence emission, tumor targeting, and surgical navigation capabilities.
- Confirmed target specificity in resected clinical NSCLC specimens.
Main Results:
- Amivantamab-IRDye800CW demonstrated strong NIR-II fluorescence emission and superior imaging performance.
- The probe achieved precise tumor targeting in vivo (TBR = 6.79 ± 0.49).
- Enabled complete resection of subcutaneous and orthotopic tumors, maintaining efficacy in heterogeneous PDX models.
- Accurately localized cancerous tissues in clinical NSCLC specimens.
Conclusions:
- Dual-targeting strategy using Amivantamab-IRDye800CW effectively mitigates tumor heterogeneity in NSCLC.
- Improves tumor localization precision and provides reliable intraoperative guidance for NSCLC surgery.
- Shows significant potential for clinical translation in improving surgical outcomes for NSCLC patients.
