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Updated: Apr 30, 2026
A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
An Octopus probe for high-performance >1,300 nm NIR-II fluorescence molecular imaging of cancer
Zhennan Peng1,2,3, Haoran Liu1,2,3,4, Huaxi Wang1,2,3
1Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong, Hong Kong 999077, China.
Abstract:
In surgical oncology, precise intraoperative delineation of malignant tumors for complete yet non-excessive resection has been challenging. Near-infrared II (NIR-II, 1,000 to 3,000 nm) imaging enables deep-tissue, high-contrast visualization, but clinical translation is limited by the lack of robust probes. Cytalux, the first clinically approved NIR-I (700 to 1,000 nm) probe for folate receptor (FR)-positive cancers, is limited in shallow imaging depth and low tumor to normal tissue contrast. Here, we present "Octopus" (OCTP), a modular multi-arm PEG-based NIR-II probe targeting FR capable of rapid and sustained tumor accumulation upon systemic administration to afford superior tumor-to-background ratios and precise margin visualization by NIR-II imaging, significantly outperforming Cytalux in mouse models. Importantly, we uncovered that NIR-II imaging in the >1,300 nm emission range under NIR-I excitation completely suppressed tissue autofluorescence, allowing unambiguous molecular imaging of residual cancerous cells at tumor margins for resection. Pharmacokinetic and toxicity studies demonstrate rapid clearance, minimal off-target accumulation, and excellent biocompatibility. OCTP enables accurate, background-free >1,300 nm fluorescence-guided tumor surgery, promising as the next-generation NIR-II molecular imaging of cancer.
Insights
A new Near-infrared II (NIR-II) probe, Octopus (OCTP), offers superior tumor visualization for surgical oncology. It enables precise, background-free margin detection, outperforming existing probes in preclinical models.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Surgical Oncology
Background:
- Intraoperative tumor delineation for complete resection is challenging in surgical oncology.
- Near-infrared II (NIR-II) imaging offers deep-tissue visualization but lacks clinical probes.
- Existing probes like Cytalux have limitations in imaging depth and contrast.
Purpose of the Study:
- To develop and evaluate a novel NIR-II molecular imaging probe for enhanced tumor visualization.
- To assess the probe's performance against clinically approved agents in preclinical cancer models.
- To demonstrate the utility of NIR-II imaging for precise tumor margin delineation.
Main Methods:
- Development of Octopus (OCTP), a modular, multi-arm PEG-based NIR-II probe targeting folate receptor (FR).
- Evaluation of OCTP's tumor accumulation, tumor-to-background ratios, and imaging performance in mouse models.
- Comparison of OCTP with Cytalux using NIR-II imaging, focusing on emission ranges >1,300 nm.
- Assessment of OCTP's pharmacokinetics, biodistribution, and toxicity.
Main Results:
- OCTP demonstrated rapid and sustained tumor accumulation with superior tumor-to-background ratios compared to Cytalux.
- NIR-II imaging in the >1,300 nm range effectively suppressed tissue autofluorescence, enabling clear visualization of residual tumor cells.
- OCTP facilitated accurate, background-free fluorescence-guided tumor margin visualization in preclinical studies.
- Pharmacokinetic and toxicity studies confirmed OCTP's rapid clearance, minimal off-target effects, and excellent biocompatibility.
Conclusions:
- OCTP is a promising next-generation NIR-II molecular imaging probe for surgical oncology.
- The probe enables accurate, background-free fluorescence-guided surgery with enhanced precision.
- OCTP significantly outperforms existing probes, addressing limitations in deep-tissue imaging and contrast.
