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High-sensitivity Detection of Micrometastases Generated by GFP Lentivirus-transduced Organoids Cultured from a Patient-derived Colon Tumor
Published on: June 14, 2018
High-precision detection and navigation surgery of colorectal cancer micrometastases
Shengjie Ma1,2, Bin Sun2,3, Mengfei Li2,3
1Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, 130012, People's Republic of China.
Abstract:
Surgical resection is an effective treatment for colorectal cancer (CRC) patients, whereas occult metastases hinder the curative effect. Currently, there is no effective method to achieve intraoperatively diagnosis of tumor-positive lymph nodes (LNs). Herein, we adopt a near-infrared-II (NIR-II) organic donor-pi-acceptor-pi-donor probe FE-2PEG, which exhibits bright fluorescence over 1100 nm, excellent photostability, blood circulation time, and biocompatibility, to achieve high-performance bioimaging with improved temporal and spatial resolution. Importantly, the FE-2PEG shows efficient passive enrichment in orthotopic CRC, metastatic mesenteric LNs, and peritoneal metastases by enhanced permeability and retention effect. Under NIR-II fluorescence-guided surgery (FGS), the peritoneal micrometastases were resected with a sensitivity of 94.51%, specificity of 86.59%, positive predictive value (PPV) of 96.57%, and negative predictive value of 79.78%. The PPV still achieves 96.07% even for micrometastases less than 3 mm. Pathological staining and NIR-II microscopy imaging proved that FE-2PEG could successfully delineate the boundary between the tumor and normal tissues. Dual-color NIR-II imaging strategy with FE-2PEG (1100 ~ 1300 nm) and PbS@CdS quantum dots (> 1500 nm) successfully protects both blood supply and normal tissues during surgery. The NIR-II-based FGS provides a promising prospect for precise intraoperative diagnosis and minimally invasive surgery of CRC.
Insights
This study introduces a new near-infrared-II (NIR-II) probe, FE-2PEG, for improved intraoperative diagnosis of colorectal cancer (CRC) lymph node metastases. NIR-II fluorescence-guided surgery (FGS) using this probe enables precise resection of even small tumors.
Area of Science:
- Biomedical Engineering
- Medical Imaging
- Oncology
Background:
- Surgical resection is key for colorectal cancer (CRC) treatment, but occult metastases limit curative outcomes.
- Intraoperative diagnosis of tumor-positive lymph nodes (LNs) remains a significant clinical challenge.
- Current diagnostic methods lack the sensitivity and specificity for detecting small or hidden metastatic sites.
Purpose of the Study:
- To develop and evaluate a novel near-infrared-II (NIR-II) organic probe, FE-2PEG, for enhanced intraoperative imaging of colorectal cancer.
- To assess the efficacy of FE-2PEG in fluorescence-guided surgery (FGS) for precise detection and resection of metastatic lesions.
- To explore a dual-color NIR-II imaging strategy for simultaneous tumor visualization and protection of vital structures.
Main Methods:
- Synthesis and characterization of the NIR-II organic probe FE-2PEG, focusing on fluorescence properties, photostability, and biocompatibility.
- In vivo evaluation of FE-2PEG for passive enrichment in orthotopic CRC models, metastatic LNs, and peritoneal metastases via the enhanced permeability and retention effect.
- Application of NIR-II FGS with FE-2PEG for resection of peritoneal micrometastases, followed by pathological analysis and dual-color imaging with quantum dots.
Main Results:
- FE-2PEG demonstrated bright fluorescence (>1100 nm), excellent photostability, and prolonged circulation time.
- High-performance bioimaging of orthotopic CRC, metastatic LNs, and peritoneal metastases was achieved with improved temporal and spatial resolution.
- NIR-II FGS using FE-2PEG achieved high sensitivity (94.51%) and specificity (86.59%) for resecting peritoneal micrometastases, with a positive predictive value (PPV) of 96.57% for lesions <3 mm.
- FE-2PEG successfully delineated tumor boundaries, and dual-color imaging protected blood supply and normal tissues.
Conclusions:
- The FE-2PEG probe offers a promising tool for high-performance intraoperative bioimaging in colorectal cancer surgery.
- NIR-II FGS enables precise diagnosis and minimally invasive resection of metastatic colorectal cancer, including micrometastases.
- The developed dual-color NIR-II imaging strategy enhances surgical safety by preserving critical anatomical structures.

