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Updated: Oct 9, 2025
A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
Tumor-Associated Immune-Cell-Mediated Tumor-Targeting Mechanism with NIR-II Fluorescence Imaging
Homan Kang1, Md Shamim2, Xiaoran Yin1,3
1Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Abstract:
The strategy of structure-inherent tumor targeting (SITT) with cyanine-based fluorophores is receiving more attention because no chemical conjugation of targeting moieties is required. However, the targeting mechanism behind SITT has not yet been well explained. Here, it is demonstrated that heptamethine-cyanine-based fluorophores possess not only targetability of tumor microenvironments without the need for additional targeting ligands but also second near-infrared spectral window (NIR-II) imaging capabilities, i.e., minimum scattering and ultralow autofluorescence. The new SITT mechanism suggests that bone-marrow-derived and/or tissue-resident/tumor-associated immune cells can be a principal target for cancer detection due to their abundance in tumoral tissues. Among the tested, SH1 provides ubiquitous tumor targetability and a high tumor-to-background ratio (TBR) ranging from 9.5 to 47 in pancreatic, breast, and lung cancer mouse models upon a single bolus intravenous injection. Furthermore, SH1 can be used to detect small cancerous tissues smaller than 2 mm in diameter in orthotopic lung cancer models. Thus, SH1 could be a promising cancer-targeting agent and have a bright future for intraoperative optical imaging and image-guided cancer surgery.
Insights
Structure-inherent tumor targeting (SITT) using cyanine dyes offers a new way to detect cancer. These dyes target immune cells in tumors, enabling early detection of small cancers for improved surgical guidance.
Area of Science:
- Biomedical Imaging
- Oncology
- Materials Science
Background:
- Structure-inherent tumor targeting (SITT) with cyanine fluorophores is a promising strategy for cancer detection, avoiding chemical conjugation.
- The precise targeting mechanism of SITT remains incompletely understood.
Purpose of the Study:
- To elucidate the mechanism of SITT using heptamethine-cyanine fluorophores.
- To evaluate the tumor targeting and imaging capabilities of these fluorophores in various cancer models.
- To explore their potential for detecting small tumors and guiding cancer surgery.
Main Methods:
- Synthesis and characterization of heptamethine-cyanine fluorophores.
- Evaluation of tumor targeting and imaging in pancreatic, breast, and lung cancer mouse models.
- Assessment of tumor-to-background ratio (TBR) and detection of small cancerous tissues (<2 mm).
Main Results:
- Heptamethine-cyanine fluorophores exhibit intrinsic tumor microenvironment targetability without ligands.
- These fluorophores offer second near-infrared (NIR-II) window imaging with minimal scattering and low autofluorescence.
- SH1 demonstrated ubiquitous tumor targeting and high TBR (9.5–47) across multiple cancer models.
- SH1 successfully detected small orthotopic lung tumors (<2 mm).
Conclusions:
- The SITT mechanism involves targeting immune cells within the tumor microenvironment.
- SH1 is a potent cancer-targeting agent with excellent imaging properties for early cancer detection.
- SH1 shows significant potential for intraoperative optical imaging and image-guided cancer surgery.
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